[{"scopus_import":"1","month":"02","language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","dataavailabilitystatement":"RNA-seq data has been deposited at GEO and are publicly available as of the date of publication. Accession numbers are listed in the key resources table. Code for the quantification of fluorescence intensity (FI) profiles in differentiated cells on stencils, as well as for model simulations, is available on GitHub (https://github.com/dbrueckner/NeuralTubeColonies, https://doi.org/10.5281/zenodo.13335390","project":[{"grant_number":"101044579","_id":"bd7e737f-d553-11ed-ba76-d69ffb5ee3aa","name":"Mechanisms of tissue size regulation in spinal cord development"},{"grant_number":"F7802","_id":"059DF620-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P02-Morphogen control of growth and pattern in the spinal cord"},{"_id":"9B9B39FA-BA93-11EA-9121-9846C619BF3A","name":"The regulatory logic of pattern formation in the vertebrate dorsal neural tube","grant_number":"SC19-011"}],"department":[{"_id":"AnKi"},{"_id":"EdHa"},{"_id":"NanoFab"}],"has_accepted_license":"1","corr_author":"1","abstract":[{"text":"Developing tissues interpret dynamic changes in morphogen activity to generate cell type diversity. To quantitatively study bone morphogenetic protein (BMP) signaling dynamics in the mouse neural tube, we developed an embryonic stem cell differentiation system tailored for growing tissues. Differentiating cells form striking self-organized patterns of dorsal neural tube cell types driven by sequential phases of BMP signaling that are observed both in vitro and in vivo. Data-driven biophysical modeling showed that these dynamics result from coupling fast negative feedback with slow positive regulation of signaling by the specification of an endogenous BMP source. Thus, in contrast to relays that propagate morphogen signaling in space, we identify a BMP signaling relay that operates in time. This mechanism allows for a rapid initial concentration-sensitive response that is robustly terminated, thereby regulating balanced sequential cell type generation. Our study provides an experimental and theoretical framework to understand how signaling dynamics are exploited in developing tissues.","lang":"eng"}],"publication_identifier":{"issn":["1534-5807"]},"citation":{"mla":"Rus, Stefanie, et al. “Self-Organized Pattern Formation in the Developing Mouse Neural Tube by a Temporal Relay of BMP Signaling.” <i>Developmental Cell</i>, vol. 60, no. 4, Cell Press, 2025, pp. 567–80, doi:<a href=\"https://doi.org/10.1016/j.devcel.2024.10.024\">10.1016/j.devcel.2024.10.024</a>.","apa":"Rus, S., Brückner, D., Minchington, T., Greunz, M., Merrin, J., Hannezo, E. B., &#38; Kicheva, A. (2025). Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling. <i>Developmental Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.devcel.2024.10.024\">https://doi.org/10.1016/j.devcel.2024.10.024</a>","chicago":"Rus, Stefanie, David Brückner, Thomas Minchington, Martina Greunz, Jack Merrin, Edouard B Hannezo, and Anna Kicheva. “Self-Organized Pattern Formation in the Developing Mouse Neural Tube by a Temporal Relay of BMP Signaling.” <i>Developmental Cell</i>. Cell Press, 2025. <a href=\"https://doi.org/10.1016/j.devcel.2024.10.024\">https://doi.org/10.1016/j.devcel.2024.10.024</a>.","short":"S. Rus, D. Brückner, T. Minchington, M. Greunz, J. Merrin, E.B. Hannezo, A. Kicheva, Developmental Cell 60 (2025) 567–580.","ama":"Rus S, Brückner D, Minchington T, et al. Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling. <i>Developmental Cell</i>. 2025;60(4):567-580. doi:<a href=\"https://doi.org/10.1016/j.devcel.2024.10.024\">10.1016/j.devcel.2024.10.024</a>","ieee":"S. Rus <i>et al.</i>, “Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling,” <i>Developmental Cell</i>, vol. 60, no. 4. Cell Press, pp. 567–580, 2025.","ista":"Rus S, Brückner D, Minchington T, Greunz M, Merrin J, Hannezo EB, Kicheva A. 2025. Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling. Developmental Cell. 60(4), 567–580."},"file_date_updated":"2025-04-16T10:54:07Z","doi":"10.1016/j.devcel.2024.10.024","article_processing_charge":"Yes (via OA deal)","title":"Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling","external_id":{"isi":["001434279000001"],"pmid":["39603235"]},"acknowledgement":"We thank A. Miller and N. Papalopulu for reagents and J. Briscoe for comments on the manuscript. Work in the A.K. lab is supported by ISTA; the European Research Council under Horizon Europe, grant 101044579; and the Austrian Science Fund (FWF), grant https://doi.org/10.55776/F78. S.L. is supported by Gesellschaft für Forschungsförderung Niederösterreich m.b.H. fellowship SC19-011. D.B.B. was supported by the NOMIS foundation as a NOMIS Fellow and by an EMBO Postdoctoral Fellowship (ALTF 343-2022).","ddc":["570"],"date_updated":"2026-10-23T22:31:30Z","_id":"18807","publisher":"Cell Press","day":"24","isi":1,"author":[{"full_name":"Rus, Stefanie","first_name":"Stefanie","orcid":"0000-0001-8703-1093","last_name":"Rus","id":"4D9EC9B6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"David","full_name":"Brückner, David","id":"e1e86031-6537-11eb-953a-f7ab92be508d","last_name":"Brückner","orcid":"0000-0001-7205-2975"},{"id":"7d1648cb-19e9-11eb-8e7a-f8c037fb3e3f","last_name":"Minchington","first_name":"Thomas","full_name":"Minchington, Thomas"},{"full_name":"Greunz, Martina","first_name":"Martina","id":"48A59534-F248-11E8-B48F-1D18A9856A87","last_name":"Greunz"},{"first_name":"Jack","full_name":"Merrin, Jack","last_name":"Merrin","orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Edouard B","full_name":"Hannezo, Edouard B","last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561"},{"orcid":"0000-0003-4509-4998","last_name":"Kicheva","id":"3959A2A0-F248-11E8-B48F-1D18A9856A87","full_name":"Kicheva, Anna","first_name":"Anna"}],"page":"567-580","das_tickbox":"1","OA_place":"publisher","supplementarymaterial":"yes","volume":60,"file":[{"success":1,"content_type":"application/pdf","file_id":"19584","creator":"dernst","file_size":6994499,"file_name":"2025_DevelopmentalCell_Lehr.pdf","access_level":"open_access","date_created":"2025-04-16T10:54:07Z","checksum":"bb58db4a908a1f4aabe4004706154541","relation":"main_file","date_updated":"2025-04-16T10:54:07Z"}],"quality_controlled":"1","pmid":1,"article_type":"original","OA_type":"hybrid","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publication":"Developmental Cell","fulldoi":"https://doi.org/10.1016/j.devcel.2024.10.024","publication_status":"published","date_published":"2025-02-24T00:00:00Z","oa":1,"date_created":"2025-01-09T11:25:47Z","type":"journal_article","issue":"4","status":"public","year":"2025","researchdata_availability":"yes","intvolume":"        60","related_material":{"record":[{"relation":"dissertation_contains","id":"19763","status":"public"}]}},{"title":"How much memory per CPU core is requested?","_id":"17139","publisher":"EuroCC Austria","ddc":["000"],"date_updated":"2024-06-17T09:40:37Z","has_accepted_license":"1","department":[{"_id":"ScienComp"}],"file_date_updated":"2024-06-17T09:36:51Z","doi":"10.25365/phaidra.463","citation":{"ama":"Schlögl A, Khalid W, Elefante S, Stadlbauer S. How much memory per CPU core is requested? In: <i>ASHPC24 - Austrian-Slovenian HPC Meeting 2024</i>. EuroCC Austria; 2024:46. doi:<a href=\"https://doi.org/10.25365/phaidra.463\">10.25365/phaidra.463</a>","short":"A. Schlögl, W. Khalid, S. Elefante, S. Stadlbauer, in:, ASHPC24 - Austrian-Slovenian HPC Meeting 2024, EuroCC Austria, 2024, p. 46.","chicago":"Schlögl, Alois, Waleed Khalid, Stefano Elefante, and Stephan Stadlbauer. “How Much Memory per CPU Core Is Requested?” In <i>ASHPC24 - Austrian-Slovenian HPC Meeting 2024</i>, 46. EuroCC Austria, 2024. <a href=\"https://doi.org/10.25365/phaidra.463\">https://doi.org/10.25365/phaidra.463</a>.","ista":"Schlögl A, Khalid W, Elefante S, Stadlbauer S. 2024. How much memory per CPU core is requested? ASHPC24 - Austrian-Slovenian HPC Meeting 2024. ASHPC: Austrian-Slovenian HPC Meeting, 46.","ieee":"A. Schlögl, W. Khalid, S. Elefante, and S. Stadlbauer, “How much memory per CPU core is requested?,” in <i>ASHPC24 - Austrian-Slovenian HPC Meeting 2024</i>, Grundlsee, Austria, 2024, p. 46.","apa":"Schlögl, A., Khalid, W., Elefante, S., &#38; Stadlbauer, S. (2024). How much memory per CPU core is requested? In <i>ASHPC24 - Austrian-Slovenian HPC Meeting 2024</i> (p. 46). Grundlsee, Austria: EuroCC Austria. <a href=\"https://doi.org/10.25365/phaidra.463\">https://doi.org/10.25365/phaidra.463</a>","mla":"Schlögl, Alois, et al. “How Much Memory per CPU Core Is Requested?” <i>ASHPC24 - Austrian-Slovenian HPC Meeting 2024</i>, EuroCC Austria, 2024, p. 46, doi:<a href=\"https://doi.org/10.25365/phaidra.463\">10.25365/phaidra.463</a>."},"publication_identifier":{"isbn":["9783200096455"]},"article_processing_charge":"No","language":[{"iso":"eng"}],"month":"06","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","oa":1,"date_published":"2024-06-13T00:00:00Z","date_created":"2024-06-14T09:06:36Z","type":"conference_abstract","year":"2024","status":"public","conference":{"location":"Grundlsee, Austria","end_date":"2024-06-13","name":"ASHPC: Austrian-Slovenian HPC Meeting","start_date":"2024-06-10"},"publication":"ASHPC24 - Austrian-Slovenian HPC Meeting 2024","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publication_status":"published","fulldoi":"https://doi.org/10.25365/phaidra.463","quality_controlled":"1","file":[{"date_created":"2024-06-17T09:36:51Z","access_level":"open_access","file_name":"2024_ASHPC_Schloegl.pdf","date_updated":"2024-06-17T09:36:51Z","relation":"main_file","checksum":"f7d3dded6df2dcdb4818904cf2e1c183","content_type":"application/pdf","file_id":"17153","success":1,"file_size":206746,"creator":"dernst"}],"day":"13","author":[{"last_name":"Schlögl","orcid":"0000-0002-5621-8100","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","first_name":"Alois","full_name":"Schlögl, Alois"},{"id":"097c0562-3cf0-11ee-8fd3-e7a79c1e2fd1","last_name":"Khalid","first_name":"Waleed","full_name":"Khalid, Waleed"},{"last_name":"Elefante","id":"490F40CE-F248-11E8-B48F-1D18A9856A87","full_name":"Elefante, Stefano","first_name":"Stefano"},{"last_name":"Stadlbauer","id":"4D0BC184-F248-11E8-B48F-1D18A9856A87","first_name":"Stephan","full_name":"Stadlbauer, Stephan"}],"page":"46"},{"project":[{"_id":"bd73af52-d553-11ed-ba76-912049f0ac7a","name":"Development of V1 interneuron diversity during swim-to-walk transition of Xenopus metamorphosis","grant_number":"FTI21-D-046"},{"name":"Development and Evolution of Tetrapod Motor Circuits","_id":"ebb66355-77a9-11ec-83b8-b8ac210a4dae","grant_number":"101041551"},{"name":"Tools for automation and feedback microscopy","_id":"c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473","grant_number":"CZI01"}],"OA_type":"green","author":[{"full_name":"Vijatovic, David","first_name":"David","last_name":"Vijatovic","id":"cf391e77-ec3c-11ea-a124-d69323410b58"},{"id":"2f73f876-f128-11eb-9611-b96b5a30cb0e","last_name":"Toma","full_name":"Toma, Florina Alexandra ","first_name":"Florina Alexandra "},{"orcid":"0009-0008-0158-4032","last_name":"Harrington","id":"a8144562-32c9-11ee-b5ce-d9800628bda2","first_name":"Zoe P","full_name":"Harrington, Zoe P"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","full_name":"Sommer, Christoph M","first_name":"Christoph M"},{"full_name":"Hauschild, Robert","first_name":"Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild"},{"full_name":"Trevisan, Alexandra J.","first_name":"Alexandra J.","last_name":"Trevisan"},{"first_name":"Phillip","full_name":"Chapman, Phillip","last_name":"Chapman"},{"last_name":"Julseth","id":"1cf464b2-dc7d-11ea-9b2f-f9b1aa9417d1","first_name":"Mara","full_name":"Julseth, Mara"},{"full_name":"Brenner-Morton, Susan","first_name":"Susan","last_name":"Brenner-Morton"},{"last_name":"Gabitto","first_name":"Mariano I.","full_name":"Gabitto, Mariano I."},{"first_name":"Jeremy S.","full_name":"Dasen, Jeremy S.","last_name":"Dasen"},{"last_name":"Bikoff","first_name":"Jay B.","full_name":"Bikoff, Jay B."},{"orcid":"0000-0001-9242-5601","id":"56BE8254-C4F0-11E9-8E45-0B23E6697425","last_name":"Sweeney","full_name":"Sweeney, Lora Beatrice Jaeger","first_name":"Lora Beatrice Jaeger"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","language":[{"iso":"eng"}],"month":"09","acknowledged_ssus":[{"_id":"Bio"}],"day":"27","main_file_link":[{"url":"https://doi.org/10.1101/2024.09.20.614050","open_access":"1"}],"OA_place":"repository","oa_version":"Preprint","date_created":"2025-04-07T08:48:28Z","oa":1,"title":"Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis","date_published":"2024-09-27T00:00:00Z","_id":"19520","status":"public","date_updated":"2025-05-14T11:40:13Z","year":"2024","acknowledgement":"We would like to thank the members of the Sweeney Lab (especially Stavros Papadopoulos and\r\nSophie Gobeil) for their contributions to this project and, in addition to the lab, Graziana Gatto\r\nand Mario de Bono, for discussion, and support. We are also grateful to Tom Jessell and Chris\r\nKintner for their scientific insight and mentorship during the conception of this project. This\r\nproject would also not have been possible with the technical support of the Matthias Nowak,\r\nVerena Mayer and the Aquatics as well as the Imaging and Optics Facility support teams\r\n(ISTA). In addition, we thank our funding sources for providing the resources to do these\r\nexperiments: FTI Strategy Lower Austria Dissertation Grant Number FT121-D-046 (D.V.);\r\nHorizon Europe ERC Starting Grant Number 101041551 (L.B.S., F.A.T. and D.V); Special\r\nResearch Program (SFB) of the Austrian Science Fund (FWF) Project number F7814-B (L.B.S);\r\nNINDS 5R35NS116858 (J.S.D); CZI grant DAF2020-225401 (DOI): 10.37921/120055ratwvi\r\n(R.H.); NIH grant number R01NS123116 (J.B.B); American Lebanese Syrian Associated\r\nCharities (ALSAC) (J.B.B.); German Academic Exchange Service (DAAD) IFI Grant Number\r\n57515251-91853472 (Z.H.); and Project A.L.S. (S.B-M.). ","type":"preprint","corr_author":"1","department":[{"_id":"LoSw"},{"_id":"TiVo"},{"_id":"Bio"},{"_id":"NiBa"}],"publication_status":"submitted","article_processing_charge":"No","fulldoi":"https://doi.org/10.1101/2024.09.20.614050","citation":{"ama":"Vijatovic D, Toma FA, Harrington ZP, et al. Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2024.09.20.614050\">10.1101/2024.09.20.614050</a>","short":"D. Vijatovic, F.A. Toma, Z.P. Harrington, C.M. Sommer, R. Hauschild, A.J. Trevisan, P. Chapman, M. Julseth, S. Brenner-Morton, M.I. Gabitto, J.S. Dasen, J.B. Bikoff, L.B. Sweeney, BioRxiv (n.d.).","chicago":"Vijatovic, David, Florina Alexandra  Toma, Zoe P Harrington, Christoph M Sommer, Robert Hauschild, Alexandra J. Trevisan, Phillip Chapman, et al. “Spinal Neuron Diversity Scales Exponentially with Swim-to-Limb Transformation during Frog Metamorphosis.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2024.09.20.614050\">https://doi.org/10.1101/2024.09.20.614050</a>.","ista":"Vijatovic D, Toma FA, Harrington ZP, Sommer CM, Hauschild R, Trevisan AJ, Chapman P, Julseth M, Brenner-Morton S, Gabitto MI, Dasen JS, Bikoff JB, Sweeney LB. Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis. bioRxiv, <a href=\"https://doi.org/10.1101/2024.09.20.614050\">10.1101/2024.09.20.614050</a>.","ieee":"D. Vijatovic <i>et al.</i>, “Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis,” <i>bioRxiv</i>. .","apa":"Vijatovic, D., Toma, F. A., Harrington, Z. P., Sommer, C. M., Hauschild, R., Trevisan, A. J., … Sweeney, L. B. (n.d.). Spinal neuron diversity scales exponentially with swim-to-limb transformation during frog metamorphosis. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2024.09.20.614050\">https://doi.org/10.1101/2024.09.20.614050</a>","mla":"Vijatovic, David, et al. “Spinal Neuron Diversity Scales Exponentially with Swim-to-Limb Transformation during Frog Metamorphosis.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2024.09.20.614050\">10.1101/2024.09.20.614050</a>."},"publication":"bioRxiv","doi":"10.1101/2024.09.20.614050","abstract":[{"lang":"eng","text":"Vertebrates exhibit a wide range of motor behaviors, ranging from swimming to complex limb-based movements. Here we take advantage of frog metamorphosis, which captures a swim-to-limb-based movement transformation during the development of a single organism, to explore changes in the underlying spinal circuits. We find that the tadpole spinal cord contains small and largely homogeneous populations of motor neurons (MNs) and V1 interneurons (V1s) at early escape swimming stages. These neuronal populations only modestly increase in number and subtype heterogeneity with the emergence of free swimming. In contrast, during frog metamorphosis and the emergence of limb movement, there is a dramatic expansion of MN and V1 interneuron number and transcriptional heterogeneity, culminating in cohorts of neurons that exhibit striking molecular similarity to mammalian motor circuits. CRISPR/Cas9-mediated gene disruption of the limb MN and V1 determinants FoxP1 and Engrailed-1, respectively, results in severe but selective deficits in tail and limb function. Our work thus demonstrates that neural diversity scales exponentially with increasing behavioral complexity and illustrates striking evolutionary conservation in the molecular organization and function of motor circuits across species."}]},{"project":[{"call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"Synaptic communication in neuronal microcircuits","grant_number":"Z00312"},{"grant_number":"P36232","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","name":"Mechanisms of GABA release in hippocampal circuits"},{"name":"Structural & functional basis of presynaptic plasticity","_id":"b1b85715-d554-11ed-a5ad-84a07fc9f18e","grant_number":"I06166"},{"name":"Zellkommunikation in Gesundheit und Krankheit","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W01205"},{"call_identifier":"FWF","name":"FWF Open Access Fund","_id":"3AC91DDA-15DF-11EA-824D-93A3E7B544D1"}],"article_number":"e3002879","oa_version":"Published Version","month":"11","language":[{"iso":"eng"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","scopus_import":"1","_id":"18603","publisher":"Public Library of Science","ddc":["570"],"date_updated":"2026-04-16T12:20:34Z","acknowledgement":"We thank Carolina Borges-Merjane, Jing-Jing Chen, Katharina Lichter, and Samuel Young for critically reading the manuscript; the Electron Microscopy Facility of ISTA, in particular Vanessa Zheden, for extensive support, advice, and experimental assistance; the Preclinical Facility of ISTA, in particular Victoria Wimmer and Michael Schunn, for experimental assistance; Florian Marr and Christina Altmutter for technical support; Alois Schlögl for help with analysis; and Eleftheria Kralli-Beller for manuscript editing. We also thank Cordelia Imig for providing Munc13-1cKO-Munc13-2/3(−/−) mutant mice. Part of the work has been published in O.K.’s thesis in partial fulfillment of the requirements for the degree of Doctor of Philosophy.\r\nThis project received funding from the European Research Council and European Union’s Horizon 2020 research and innovation programme (ERC 692692 to P.J.; https://cordis.europa.eu/project/id/692692/de) and from the Fond zur Förderung der Wissenschaftlichen Forschung (Z312-B27 Wittgenstein award to P.J., https://www.fwf.ac.at/en/funding/portfolio/projects/fwf-wittgenstein-award; W1205-B09 and P36232-B to P.J., https://www.fwf.ac.at/en/funding; I6166-B to R.S.; https://www.fwf.ac.at/en/funding). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","external_id":{"pmid":["39556620"],"isi":["001358568700003"]},"APC_amount":"6248,82 EUR","title":"Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons","DOAJ_listed":"1","article_processing_charge":"Yes","doi":"10.1371/journal.pbio.3002879","citation":{"mla":"Kim, Olena, et al. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber Boutons.” <i>PLoS Biology</i>, vol. 22, no. 11, e3002879, Public Library of Science, 2024, doi:<a href=\"https://doi.org/10.1371/journal.pbio.3002879\">10.1371/journal.pbio.3002879</a>.","apa":"Kim, O., Okamoto, Y., Kaufmann, W., Brose, N., Shigemoto, R., &#38; Jonas, P. M. (2024). Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. <i>PLoS Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pbio.3002879\">https://doi.org/10.1371/journal.pbio.3002879</a>","short":"O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, P.M. Jonas, PLoS Biology 22 (2024).","chicago":"Kim, Olena, Yuji Okamoto, Walter Kaufmann, Nils Brose, Ryuichi Shigemoto, and Peter M Jonas. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber Boutons.” <i>PLoS Biology</i>. Public Library of Science, 2024. <a href=\"https://doi.org/10.1371/journal.pbio.3002879\">https://doi.org/10.1371/journal.pbio.3002879</a>.","ama":"Kim O, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. <i>PLoS Biology</i>. 2024;22(11). doi:<a href=\"https://doi.org/10.1371/journal.pbio.3002879\">10.1371/journal.pbio.3002879</a>","ieee":"O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, and P. M. Jonas, “Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons,” <i>PLoS Biology</i>, vol. 22, no. 11. Public Library of Science, 2024.","ista":"Kim O, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. 2024. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. PLoS Biology. 22(11), e3002879."},"file_date_updated":"2024-12-03T08:56:53Z","abstract":[{"text":"It is widely believed that information storage in neuronal circuits involves nanoscopic structural changes at synapses, resulting in the formation of synaptic engrams. However, direct evidence for this hypothesis is lacking. To test this conjecture, we combined chemical potentiation, functional analysis by paired pre-postsynaptic recordings, and structural analysis by electron microscopy (EM) and freeze-fracture replica labeling (FRL) at the rodent hippocampal mossy fiber synapse, a key synapse in the trisynaptic circuit of the hippocampus. Biophysical analysis of synaptic transmission revealed that forskolin-induced chemical potentiation increased the readily releasable vesicle pool size and vesicular release probability by 146% and 49%, respectively. Structural analysis of mossy fiber synapses by EM and FRL demonstrated an increase in the number of vesicles close to the plasma membrane and the number of clusters of the priming protein Munc13-1, indicating an increase in the number of both docked and primed vesicles. Furthermore, FRL analysis revealed a significant reduction of the distance between Munc13-1 and CaV2.1 Ca2+ channels, suggesting reconfiguration of the channel-vesicle coupling nanotopography. Our results indicate that presynaptic plasticity is associated with structural reorganization of active zones. We propose that changes in potential nanoscopic organization at synaptic vesicle release sites may be correlates of learning and memory at a plastic central synapse.","lang":"eng"}],"publication_identifier":{"issn":["1544-9173"],"eissn":["1545-7885"]},"corr_author":"1","has_accepted_license":"1","department":[{"_id":"PeJo"},{"_id":"EM-Fac"},{"_id":"RySh"}],"OA_type":"gold","article_type":"original","pmid":1,"quality_controlled":"1","file":[{"creator":"dernst","file_size":3057631,"success":1,"content_type":"application/pdf","file_id":"18608","date_updated":"2024-12-03T08:56:53Z","relation":"main_file","checksum":"7de2dcb50deb65dde05c80082bb85a82","file_name":"2024_PloSBio_Kim.pdf","date_created":"2024-12-03T08:56:53Z","access_level":"open_access"}],"volume":22,"ec_funded":1,"OA_place":"publisher","author":[{"full_name":"Kim, 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Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18296\">10.15479/AT:ISTA:18296</a>.","apa":"Kim, O. (2024). Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:18296\">https://doi.org/10.15479/AT:ISTA:18296</a>","ieee":"O. Kim, “Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons.” Institute of Science and Technology Austria, 2024.","ista":"Kim O. 2024. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:18296\">10.15479/AT:ISTA:18296</a>.","short":"O. Kim, (2024).","chicago":"Kim, Olena. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber Boutons.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/AT:ISTA:18296\">https://doi.org/10.15479/AT:ISTA:18296</a>.","ama":"Kim O. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. 2024. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18296\">10.15479/AT:ISTA:18296</a>"},"file_date_updated":"2024-10-11T10:04:23Z","abstract":[{"lang":"eng","text":"It is widely believed that information storage in neuronal circuits involves nanoscopic structural changes at synapses, resulting in the formation of synaptic engrams. However, direct evidence for this hypothesis is lacking. 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Furthermore, FRL analysis revealed a significant reduction of the distance between Munc13-1 and CaV2.1 Ca2+ channels, suggesting reconfiguration of the channel-vesicle coupling nanotopography. Our results indicate that presynaptic plasticity is associated with structural reorganization of active zones. We propose that changes in potential nanoscopic organization at synaptic vesicle release sites may be correlates of learning and memory at a plastic central synapse."}],"article_processing_charge":"No","title":"Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons","_id":"18296","publisher":"Institute of Science and Technology Austria","date_updated":"2026-09-14T08:48:01Z","ddc":["570"],"user_id":"68b8ca59-c5b3-11ee-8790-cd641c68093d","month":"10","oa_version":"Submitted Version","project":[{"call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692"}]},{"oa_version":"Published Version","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","month":"12","language":[{"iso":"eng"}],"scopus_import":"1","article_processing_charge":"No","file_date_updated":"2024-12-03T14:07:04Z","citation":{"apa":"Lauwereyns, J., Bajramovic, J., Bert, B., Camenzind, S., De Kock, J., Elezović, A., … Ahluwalia, A. (2024). Toward a common interpretation of the 3Rs principles in animal research. <i>Lab Animal</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41684-024-01476-2\">https://doi.org/10.1038/s41684-024-01476-2</a>","mla":"Lauwereyns, Jan, et al. “Toward a Common Interpretation of the 3Rs Principles in Animal Research.” <i>Lab Animal</i>, vol. 53, Springer Nature, 2024, pp. 347–50, doi:<a href=\"https://doi.org/10.1038/s41684-024-01476-2\">10.1038/s41684-024-01476-2</a>.","ama":"Lauwereyns J, Bajramovic J, Bert B, et al. Toward a common interpretation of the 3Rs principles in animal research. <i>Lab Animal</i>. 2024;53:347-350. doi:<a href=\"https://doi.org/10.1038/s41684-024-01476-2\">10.1038/s41684-024-01476-2</a>","short":"J. Lauwereyns, J. Bajramovic, B. Bert, S. Camenzind, J. De Kock, A. Elezović, S. Erden, F. Gonzalez-Uarquin, Y.I. Ulman, O.I. Hoffmann, M. Kitsara, N. Kostomitsopoulos, W. Neuhaus, B. Petit-Demouliere, S. Pollo, B. Riso, S. Schober, A. Sotiropoulos, A. Thomas, A. Vitale, D. Wilflingseder, A. Ahluwalia, Lab Animal 53 (2024) 347–350.","chicago":"Lauwereyns, Jan, Jeffrey Bajramovic, Bettina Bert, Samuel Camenzind, Joery De Kock, Alisa Elezović, Sevilay Erden, et al. “Toward a Common Interpretation of the 3Rs Principles in Animal Research.” <i>Lab Animal</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41684-024-01476-2\">https://doi.org/10.1038/s41684-024-01476-2</a>.","ista":"Lauwereyns J, Bajramovic J, Bert B, Camenzind S, De Kock J, Elezović A, Erden S, Gonzalez-Uarquin F, Ulman YI, Hoffmann OI, Kitsara M, Kostomitsopoulos N, Neuhaus W, Petit-Demouliere B, Pollo S, Riso B, Schober S, Sotiropoulos A, Thomas A, Vitale A, Wilflingseder D, Ahluwalia A. 2024. Toward a common interpretation of the 3Rs principles in animal research. Lab Animal. 53, 347–350.","ieee":"J. Lauwereyns <i>et al.</i>, “Toward a common interpretation of the 3Rs principles in animal research,” <i>Lab Animal</i>, vol. 53. 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We acknowledge the input and advice from Dr. Susanna Louhimies.","external_id":{"pmid":["39548348"],"isi":["001355264100001"]},"title":"Toward a common interpretation of the 3Rs principles in animal research","OA_place":"publisher","das_tickbox":"0","page":"347-350","author":[{"last_name":"Lauwereyns","first_name":"Jan","full_name":"Lauwereyns, Jan"},{"last_name":"Bajramovic","first_name":"Jeffrey","full_name":"Bajramovic, Jeffrey"},{"last_name":"Bert","full_name":"Bert, Bettina","first_name":"Bettina"},{"last_name":"Camenzind","full_name":"Camenzind, Samuel","first_name":"Samuel"},{"full_name":"De Kock, Joery","first_name":"Joery","last_name":"De Kock"},{"full_name":"Elezović, Alisa","first_name":"Alisa","last_name":"Elezović"},{"first_name":"Sevilay","full_name":"Erden, Sevilay","last_name":"Erden"},{"full_name":"Gonzalez-Uarquin, Fernando","first_name":"Fernando","last_name":"Gonzalez-Uarquin"},{"full_name":"Ulman, Yesim Isil","first_name":"Yesim Isil","last_name":"Ulman"},{"first_name":"Orsolya Ivett","full_name":"Hoffmann, Orsolya Ivett","last_name":"Hoffmann"},{"last_name":"Kitsara","first_name":"Maria","full_name":"Kitsara, Maria"},{"last_name":"Kostomitsopoulos","full_name":"Kostomitsopoulos, Nikolaos","first_name":"Nikolaos"},{"full_name":"Neuhaus, Winfried","first_name":"Winfried","last_name":"Neuhaus"},{"last_name":"Petit-Demouliere","first_name":"Benoit","full_name":"Petit-Demouliere, Benoit"},{"last_name":"Pollo","first_name":"Simone","full_name":"Pollo, Simone"},{"full_name":"Riso, Brígida","first_name":"Brígida","last_name":"Riso"},{"last_name":"Schober","id":"80b0a0ef-4b9f-11ec-b119-8d9d94c4a1d8","full_name":"Schober, Sophie","first_name":"Sophie"},{"last_name":"Sotiropoulos","first_name":"Athanassia","full_name":"Sotiropoulos, Athanassia"},{"first_name":"Aurélie","full_name":"Thomas, Aurélie","last_name":"Thomas"},{"last_name":"Vitale","full_name":"Vitale, Augusto","first_name":"Augusto"},{"last_name":"Wilflingseder","full_name":"Wilflingseder, Doris","first_name":"Doris"},{"first_name":"Arti","full_name":"Ahluwalia, Arti","last_name":"Ahluwalia"}],"isi":1,"day":"01","article_type":"letter_note","OA_type":"hybrid","pmid":1,"quality_controlled":"1","file":[{"date_created":"2024-12-03T14:07:04Z","access_level":"open_access","file_name":"2024_LabAnimal_Lauwereyns.pdf","relation":"main_file","date_updated":"2024-12-03T14:07:04Z","checksum":"67fc140f761581a291591f075e49b88d","content_type":"application/pdf","file_id":"18614","success":1,"file_size":967252,"creator":"dernst"}],"volume":53,"supplementarymaterial":"no","publication_status":"published","fulldoi":"https://doi.org/10.1038/s41684-024-01476-2","publication":"Lab Animal","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"intvolume":"        53","researchdata_availability":"no","status":"public","year":"2024","type":"journal_article","date_created":"2024-11-24T23:01:49Z","oa":1,"date_published":"2024-12-01T00:00:00Z"},{"oa_version":"None","month":"11","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","language":[{"iso":"eng"}],"scopus_import":"1","article_processing_charge":"No","publication_identifier":{"issn":["0261-1929"],"eissn":["2632-3559"]},"doi":"10.1177/02611929241286024","citation":{"mla":"Kitsara, Maria, et al. “Introducing the COST Action ‘Improving the Quality of Biomedical Science with 3Rs Concepts’ (IMPROVE).” <i>Alternatives to Laboratory Animals</i>, vol. 52, no. 6, SAGE Publications, 2024, pp. 326–33, doi:<a href=\"https://doi.org/10.1177/02611929241286024\">10.1177/02611929241286024</a>.","apa":"Kitsara, M., Smajlhodžić-Deljo, M., Gurbeta Pokvic, L., Bert, B., Bubalo, N., Erden, S., … Neuhaus, W. (2024). Introducing the COST action ‘Improving the Quality of Biomedical Science with 3Rs Concepts’ (IMPROVE). <i>Alternatives to Laboratory Animals</i>. SAGE Publications. <a href=\"https://doi.org/10.1177/02611929241286024\">https://doi.org/10.1177/02611929241286024</a>","ieee":"M. Kitsara <i>et al.</i>, “Introducing the COST action ‘Improving the Quality of Biomedical Science with 3Rs Concepts’ (IMPROVE),” <i>Alternatives to Laboratory Animals</i>, vol. 52, no. 6. SAGE Publications, pp. 326–333, 2024.","ista":"Kitsara M, Smajlhodžić-Deljo M, Gurbeta Pokvic L, Bert B, Bubalo N, Erden S, Franco NH, Chirico G, Gómez Raja J, Gonzalez-Uarquin F, Lang A, Linklater N, Mojsova S, Olsson IAS, Sandvig I, Schaffert A, Schmit M, Schober S, Sevastre B, Wilflingseder D, Ahluwalia A, Neuhaus W. 2024. Introducing the COST action ‘Improving the Quality of Biomedical Science with 3Rs Concepts’ (IMPROVE). Alternatives to Laboratory Animals. 52(6), 326–333.","chicago":"Kitsara, Maria, Merima Smajlhodžić-Deljo, Lejla Gurbeta Pokvic, Bettina Bert, Nataliia Bubalo, Sevilay Erden, Nuno Henrique Franco, et al. “Introducing the COST Action ‘Improving the Quality of Biomedical Science with 3Rs Concepts’ (IMPROVE).” <i>Alternatives to Laboratory Animals</i>. SAGE Publications, 2024. <a href=\"https://doi.org/10.1177/02611929241286024\">https://doi.org/10.1177/02611929241286024</a>.","short":"M. Kitsara, M. Smajlhodžić-Deljo, L. Gurbeta Pokvic, B. Bert, N. Bubalo, S. Erden, N.H. Franco, G. Chirico, J. Gómez Raja, F. Gonzalez-Uarquin, A. Lang, N. Linklater, S. Mojsova, I.A.S. Olsson, I. Sandvig, A. Schaffert, M. Schmit, S. Schober, B. Sevastre, D. Wilflingseder, A. Ahluwalia, W. Neuhaus, Alternatives to Laboratory Animals 52 (2024) 326–333.","ama":"Kitsara M, Smajlhodžić-Deljo M, Gurbeta Pokvic L, et al. Introducing the COST action ‘Improving the Quality of Biomedical Science with 3Rs Concepts’ (IMPROVE). <i>Alternatives to Laboratory Animals</i>. 2024;52(6):326-333. doi:<a href=\"https://doi.org/10.1177/02611929241286024\">10.1177/02611929241286024</a>"},"department":[{"_id":"PreCl"}],"date_updated":"2026-09-17T10:30:08Z","_id":"18310","publisher":"SAGE Publications","external_id":{"isi":["001348633700007"],"pmid":["39333027"]},"title":"Introducing the COST action ‘Improving the Quality of Biomedical Science with 3Rs Concepts’ (IMPROVE)","page":"326-333","das_tickbox":"0","isi":1,"author":[{"full_name":"Kitsara, Maria","first_name":"Maria","last_name":"Kitsara"},{"last_name":"Smajlhodžić-Deljo","first_name":"Merima","full_name":"Smajlhodžić-Deljo, Merima"},{"last_name":"Gurbeta Pokvic","full_name":"Gurbeta Pokvic, Lejla","first_name":"Lejla"},{"full_name":"Bert, Bettina","first_name":"Bettina","last_name":"Bert"},{"last_name":"Bubalo","first_name":"Nataliia","full_name":"Bubalo, Nataliia"},{"first_name":"Sevilay","full_name":"Erden, Sevilay","last_name":"Erden"},{"full_name":"Franco, Nuno Henrique","first_name":"Nuno Henrique","last_name":"Franco"},{"full_name":"Chirico, Giuseppe","first_name":"Giuseppe","last_name":"Chirico"},{"first_name":"Jonathan","full_name":"Gómez Raja, Jonathan","last_name":"Gómez Raja"},{"first_name":"Fernando","full_name":"Gonzalez-Uarquin, Fernando","last_name":"Gonzalez-Uarquin"},{"last_name":"Lang","first_name":"Annemarie","full_name":"Lang, Annemarie"},{"last_name":"Linklater","full_name":"Linklater, Nicole","first_name":"Nicole"},{"full_name":"Mojsova, Sandra","first_name":"Sandra","last_name":"Mojsova"},{"last_name":"Olsson","full_name":"Olsson, I. Anna S.","first_name":"I. Anna S."},{"full_name":"Sandvig, Ioanna","first_name":"Ioanna","last_name":"Sandvig"},{"last_name":"Schaffert","full_name":"Schaffert, Alexandra","first_name":"Alexandra"},{"first_name":"Marthe","full_name":"Schmit, Marthe","last_name":"Schmit"},{"first_name":"Sophie","full_name":"Schober, Sophie","id":"80b0a0ef-4b9f-11ec-b119-8d9d94c4a1d8","last_name":"Schober"},{"first_name":"Bogdan","full_name":"Sevastre, Bogdan","last_name":"Sevastre"},{"last_name":"Wilflingseder","full_name":"Wilflingseder, Doris","first_name":"Doris"},{"first_name":"Arti","full_name":"Ahluwalia, Arti","last_name":"Ahluwalia"},{"first_name":"Winfried","full_name":"Neuhaus, Winfried","last_name":"Neuhaus"}],"day":"01","pmid":1,"OA_type":"closed access","article_type":"original","quality_controlled":"1","supplementarymaterial":"no","volume":52,"fulldoi":"https://doi.org/10.1177/02611929241286024","publication_status":"published","publication":"Alternatives to Laboratory Animals","researchdata_availability":"no","year":"2024","status":"public","intvolume":"        52","type":"journal_article","issue":"6","date_created":"2024-10-13T22:01:51Z","date_published":"2024-11-01T00:00:00Z"},{"type":"journal_article","researchdata_availability":"yes","year":"2024","status":"public","intvolume":"        20","related_material":{"link":[{"description":"News on ISTA Website","relation":"press_release","url":"https://ista.ac.at/en/news/stranger-than-friction-a-force-initiating-life/"}]},"date_published":"2024-02-01T00:00:00Z","oa":1,"date_created":"2024-01-21T23:00:57Z","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publication":"Nature Physics","fulldoi":"https://doi.org/10.1038/s41567-023-02302-1","publication_status":"published","file":[{"checksum":"7891ebe7c900ae47469ab127031dd1ec","relation":"main_file","date_updated":"2024-07-16T12:12:43Z","file_name":"2024_NaturePhysics_CaballeroMancebo.pdf","access_level":"open_access","date_created":"2024-07-16T12:12:43Z","creator":"dernst","file_size":9897883,"success":1,"file_id":"17267","content_type":"application/pdf"}],"quality_controlled":"1","pmid":1,"article_type":"original","supplementarymaterial":"yes","volume":20,"page":"310-321","das_tickbox":"1","day":"01","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"NanoFab"}],"isi":1,"author":[{"orcid":"0000-0002-5223-3346","last_name":"Caballero Mancebo","id":"2F1E1758-F248-11E8-B48F-1D18A9856A87","first_name":"Silvia","full_name":"Caballero Mancebo, Silvia"},{"full_name":"Shinde, Rushikesh","first_name":"Rushikesh","last_name":"Shinde"},{"full_name":"Bolger-Munro, Madison","first_name":"Madison","id":"516F03FA-93A3-11EA-A7C5-D6BE3DDC885E","last_name":"Bolger-Munro","orcid":"0000-0002-8176-4824"},{"first_name":"Matilda","full_name":"Peruzzo, Matilda","id":"3F920B30-F248-11E8-B48F-1D18A9856A87","last_name":"Peruzzo","orcid":"0000-0002-3415-4628"},{"last_name":"Szep","id":"4BFB7762-F248-11E8-B48F-1D18A9856A87","full_name":"Szep, Gregory","first_name":"Gregory"},{"first_name":"Irene","full_name":"Steccari, Irene","last_name":"Steccari","id":"2705C766-9FE2-11EA-B224-C6773DDC885E"},{"last_name":"Labrousse Arias","id":"CD573DF4-9ED3-11E9-9D77-3223E6697425","first_name":"David","full_name":"Labrousse Arias, David"},{"full_name":"Zheden, Vanessa","first_name":"Vanessa","last_name":"Zheden","orcid":"0000-0002-9438-4783","id":"39C5A68A-F248-11E8-B48F-1D18A9856A87"},{"id":"4515C308-F248-11E8-B48F-1D18A9856A87","last_name":"Merrin","orcid":"0000-0001-5145-4609","first_name":"Jack","full_name":"Merrin, Jack"},{"last_name":"Callan-Jones","full_name":"Callan-Jones, Andrew","first_name":"Andrew"},{"full_name":"Voituriez, Raphaël","first_name":"Raphaël","last_name":"Voituriez"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","last_name":"Heisenberg","full_name":"Heisenberg, Carl-Philipp J","first_name":"Carl-Philipp J"}],"external_id":{"isi":["001138880800005"],"pmid":["38370025"]},"acknowledgement":"We would like to thank A. McDougall, E. Hannezo and the Heisenberg lab for fruitful discussions and reagents. We also thank E. Munro for the iMyo-YFP and Bra>iMyo-mScarlet constructs. This research was supported by the Scientific Service Units of the Institute of Science and Technology Austria through resources provided by the Electron Microscopy Facility, Imaging and Optics Facility and the Nanofabrication Facility. This work was supported by a Joint Project Grant from the FWF (I 3601-B27).","ddc":["530"],"date_updated":"2026-10-01T08:33:51Z","publisher":"Springer Nature","_id":"14846","title":"Friction forces determine cytoplasmic reorganization and shape changes of ascidian oocytes upon fertilization","abstract":[{"text":"Contraction and flow of the actin cell cortex have emerged as a common principle by which cells reorganize their cytoplasm and take shape. However, how these cortical flows interact with adjacent cytoplasmic components, changing their form and localization, and how this affects cytoplasmic organization and cell shape remains unclear. Here we show that in ascidian oocytes, the cooperative activities of cortical actomyosin flows and deformation of the adjacent mitochondria-rich myoplasm drive oocyte cytoplasmic reorganization and shape changes following fertilization. We show that vegetal-directed cortical actomyosin flows, established upon oocyte fertilization, lead to both the accumulation of cortical actin at the vegetal pole of the zygote and compression and local buckling of the adjacent elastic solid-like myoplasm layer due to friction forces generated at their interface. Once cortical flows have ceased, the multiple myoplasm buckles resolve into one larger buckle, which again drives the formation of the contraction pole—a protuberance of the zygote’s vegetal pole where maternal mRNAs accumulate. Thus, our findings reveal a mechanism where cortical actomyosin network flows determine cytoplasmic reorganization and cell shape by deforming adjacent cytoplasmic components through friction forces.","lang":"eng"}],"publication_identifier":{"eissn":["1745-2481"],"issn":["1745-2473"]},"file_date_updated":"2024-07-16T12:12:43Z","doi":"10.1038/s41567-023-02302-1","citation":{"apa":"Caballero Mancebo, S., Shinde, R., Bolger-Munro, M., Peruzzo, M., Szep, G., Steccari, I., … Heisenberg, C.-P. J. (2024). Friction forces determine cytoplasmic reorganization and shape changes of ascidian oocytes upon fertilization. <i>Nature Physics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41567-023-02302-1\">https://doi.org/10.1038/s41567-023-02302-1</a>","mla":"Caballero Mancebo, Silvia, et al. “Friction Forces Determine Cytoplasmic Reorganization and Shape Changes of Ascidian Oocytes upon Fertilization.” <i>Nature Physics</i>, vol. 20, Springer Nature, 2024, pp. 310–21, doi:<a href=\"https://doi.org/10.1038/s41567-023-02302-1\">10.1038/s41567-023-02302-1</a>.","ama":"Caballero Mancebo S, Shinde R, Bolger-Munro M, et al. Friction forces determine cytoplasmic reorganization and shape changes of ascidian oocytes upon fertilization. <i>Nature Physics</i>. 2024;20:310-321. doi:<a href=\"https://doi.org/10.1038/s41567-023-02302-1\">10.1038/s41567-023-02302-1</a>","chicago":"Caballero Mancebo, Silvia, Rushikesh Shinde, Madison Bolger-Munro, Matilda Peruzzo, Gregory Szep, Irene Steccari, David Labrousse Arias, et al. “Friction Forces Determine Cytoplasmic Reorganization and Shape Changes of Ascidian Oocytes upon Fertilization.” <i>Nature Physics</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41567-023-02302-1\">https://doi.org/10.1038/s41567-023-02302-1</a>.","short":"S. Caballero Mancebo, R. Shinde, M. Bolger-Munro, M. Peruzzo, G. Szep, I. Steccari, D. Labrousse Arias, V. Zheden, J. Merrin, A. Callan-Jones, R. Voituriez, C.-P.J. Heisenberg, Nature Physics 20 (2024) 310–321.","ista":"Caballero Mancebo S, Shinde R, Bolger-Munro M, Peruzzo M, Szep G, Steccari I, Labrousse Arias D, Zheden V, Merrin J, Callan-Jones A, Voituriez R, Heisenberg C-PJ. 2024. Friction forces determine cytoplasmic reorganization and shape changes of ascidian oocytes upon fertilization. Nature Physics. 20, 310–321.","ieee":"S. Caballero Mancebo <i>et al.</i>, “Friction forces determine cytoplasmic reorganization and shape changes of ascidian oocytes upon fertilization,” <i>Nature Physics</i>, vol. 20. Springer Nature, pp. 310–321, 2024."},"article_processing_charge":"Yes (in subscription journal)","department":[{"_id":"CaHe"},{"_id":"JoFi"},{"_id":"MiSi"},{"_id":"EM-Fac"},{"_id":"NanoFab"}],"has_accepted_license":"1","corr_author":"1","project":[{"call_identifier":"FWF","name":"Control of embryonic cleavage pattern","_id":"2646861A-B435-11E9-9278-68D0E5697425","grant_number":"I03601"}],"dataavailabilitystatement":"Source data are provided with this paper. All other data supporting the findings of this study are available from the corresponding author on request","oa_version":"Published Version","scopus_import":"1","language":[{"iso":"eng"}],"month":"02","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345"},{"ec_funded":1,"page":"171-182.e8","das_tickbox":"1","isi":1,"author":[{"full_name":"Arslan, Feyza N","first_name":"Feyza N","id":"49DA7910-F248-11E8-B48F-1D18A9856A87","last_name":"Arslan","orcid":"0000-0001-5809-9566"},{"last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","first_name":"Edouard B"},{"last_name":"Merrin","orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87","full_name":"Merrin, Jack","first_name":"Jack"},{"id":"462D4284-F248-11E8-B48F-1D18A9856A87","last_name":"Loose","orcid":"0000-0001-7309-9724","first_name":"Martin","full_name":"Loose, Martin"},{"first_name":"Carl-Philipp J","full_name":"Heisenberg, Carl-Philipp J","last_name":"Heisenberg","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566"}],"day":"08","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"pmid":1,"article_type":"original","file":[{"date_updated":"2024-01-16T10:53:31Z","relation":"main_file","checksum":"51220b76d72a614208f84bdbfbaf9b72","file_name":"2024_CurrentBiology_Arslan.pdf","date_created":"2024-01-16T10:53:31Z","access_level":"open_access","creator":"dernst","file_size":5183861,"success":1,"file_id":"14813","content_type":"application/pdf"}],"quality_controlled":"1","supplementarymaterial":"yes","volume":34,"fulldoi":"https://doi.org/10.1016/j.cub.2023.11.067","publication_status":"published","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publication":"Current Biology","researchdata_availability":"upon request","year":"2024","status":"public","intvolume":"        34","type":"journal_article","issue":"1","date_created":"2024-01-14T23:00:56Z","date_published":"2024-01-08T00:00:00Z","oa":1,"oa_version":"Published Version","month":"01","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","language":[{"iso":"eng"}],"scopus_import":"1","project":[{"grant_number":"742573","call_identifier":"H2020","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","_id":"260F1432-B435-11E9-9278-68D0E5697425"}],"dataavailabilitystatement":"All original microscopy data any additional information reported in this paper is available from the lead contact upon request. All original code is available from the lead contact upon request","article_processing_charge":"Yes (via OA deal)","publication_identifier":{"eissn":["1879-0445"],"issn":["0960-9822"]},"abstract":[{"text":"Metazoan development relies on the formation and remodeling of cell-cell contacts. Dynamic reorganization of adhesion receptors and the actomyosin cell cortex in space and time plays a central role in cell-cell contact formation and maturation. Nevertheless, how this process is mechanistically achieved when new contacts are formed remains unclear. Here, by building a biomimetic assay composed of progenitor cells adhering to supported lipid bilayers functionalized with E-cadherin ectodomains, we show that cortical F-actin flows, driven by the depletion of myosin-2 at the cell contact center, mediate the dynamic reorganization of adhesion receptors and cell cortex at the contact. E-cadherin-dependent downregulation of the small GTPase RhoA at the forming contact leads to both a depletion of myosin-2 and a decrease of F-actin at the contact center. At the contact rim, in contrast, myosin-2 becomes enriched by the retraction of bleb-like protrusions, resulting in a cortical tension gradient from the contact rim to its center. This tension gradient, in turn, triggers centrifugal F-actin flows, leading to further accumulation of F-actin at the contact rim and the progressive redistribution of E-cadherin from the contact center to the rim. Eventually, this combination of actomyosin downregulation and flows at the contact determines the characteristic molecular organization, with E-cadherin and F-actin accumulating at the contact rim, where they are needed to mechanically link the contractile cortices of the adhering cells.","lang":"eng"}],"citation":{"ista":"Arslan FN, Hannezo EB, Merrin J, Loose M, Heisenberg C-PJ. 2024. Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts. Current Biology. 34(1), 171–182.e8.","ieee":"F. N. Arslan, E. B. Hannezo, J. Merrin, M. Loose, and C.-P. J. Heisenberg, “Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts,” <i>Current Biology</i>, vol. 34, no. 1. Elsevier, p. 171–182.e8, 2024.","ama":"Arslan FN, Hannezo EB, Merrin J, Loose M, Heisenberg C-PJ. Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts. <i>Current Biology</i>. 2024;34(1):171-182.e8. doi:<a href=\"https://doi.org/10.1016/j.cub.2023.11.067\">10.1016/j.cub.2023.11.067</a>","short":"F.N. Arslan, E.B. Hannezo, J. Merrin, M. Loose, C.-P.J. Heisenberg, Current Biology 34 (2024) 171–182.e8.","chicago":"Arslan, Feyza N, Edouard B Hannezo, Jack Merrin, Martin Loose, and Carl-Philipp J Heisenberg. “Adhesion-Induced Cortical Flows Pattern E-Cadherin-Mediated Cell Contacts.” <i>Current Biology</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.cub.2023.11.067\">https://doi.org/10.1016/j.cub.2023.11.067</a>.","apa":"Arslan, F. N., Hannezo, E. B., Merrin, J., Loose, M., &#38; Heisenberg, C.-P. J. (2024). Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts. <i>Current Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cub.2023.11.067\">https://doi.org/10.1016/j.cub.2023.11.067</a>","mla":"Arslan, Feyza N., et al. “Adhesion-Induced Cortical Flows Pattern E-Cadherin-Mediated Cell Contacts.” <i>Current Biology</i>, vol. 34, no. 1, Elsevier, 2024, p. 171–182.e8, doi:<a href=\"https://doi.org/10.1016/j.cub.2023.11.067\">10.1016/j.cub.2023.11.067</a>."},"file_date_updated":"2024-01-16T10:53:31Z","doi":"10.1016/j.cub.2023.11.067","corr_author":"1","department":[{"_id":"CaHe"},{"_id":"EdHa"},{"_id":"MaLo"},{"_id":"NanoFab"}],"has_accepted_license":"1","ddc":["570"],"date_updated":"2026-10-01T08:33:05Z","publisher":"Elsevier","_id":"14795","external_id":{"pmid":["38134934"],"isi":["001154500400001"]},"acknowledgement":"We are grateful to Edwin Munro for their feedback and help with the single particle analysis. We thank members of the Heisenberg and Loose labs for their help and feedback on the manuscript, notably Xin Tong for making the PCS2-mCherry-AHPH plasmid. Finally, we thank the Aquatics and Imaging & Optics facilities of ISTA for their continuous support, especially Yann Cesbron for assistance with the laser cutter. This work was supported by an ERC\r\nAdvanced Grant (MECSPEC) to C.-P.H.","title":"Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts"},{"tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publication":"Development","fulldoi":"https://doi.org/10.1242/dev.202316","publication_status":"published","type":"journal_article","issue":"4","researchdata_availability":"yes","status":"public","year":"2024","intvolume":"       151","related_material":{"record":[{"relation":"research_data","id":"14926","status":"public"}]},"date_published":"2024-02-01T00:00:00Z","oa":1,"date_created":"2024-03-03T23:00:50Z","page":"1-18","das_tickbox":"1","ec_funded":1,"day":"01","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"isi":1,"author":[{"last_name":"Schauer","orcid":"0000-0001-7659-9142","id":"30A536BA-F248-11E8-B48F-1D18A9856A87","first_name":"Alexandra","full_name":"Schauer, Alexandra"},{"id":"4362B3C2-F248-11E8-B48F-1D18A9856A87","last_name":"Pranjic-Ferscha","first_name":"Kornelija","full_name":"Pranjic-Ferscha, Kornelija"},{"full_name":"Hauschild, Robert","first_name":"Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild"},{"full_name":"Heisenberg, Carl-Philipp J","first_name":"Carl-Philipp J","last_name":"Heisenberg","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566"}],"file":[{"creator":"dernst","file_size":14839986,"success":1,"content_type":"application/pdf","file_id":"15050","relation":"main_file","date_updated":"2024-03-04T07:24:43Z","checksum":"6961ea10012bf0d266681f9628bb8f13","file_name":"2024_Development_Schauer.pdf","date_created":"2024-03-04T07:24:43Z","access_level":"open_access"}],"quality_controlled":"1","pmid":1,"article_type":"original","supplementarymaterial":"yes","volume":151,"abstract":[{"lang":"eng","text":"Embryogenesis results from the coordinated activities of different signaling pathways controlling cell fate specification and morphogenesis. In vertebrate gastrulation, both Nodal and BMP signaling play key roles in germ layer specification and morphogenesis, yet their interplay to coordinate embryo patterning with morphogenesis is still insufficiently understood. Here, we took a reductionist approach using zebrafish embryonic explants to study the coordination of Nodal and BMP signaling for embryo patterning and morphogenesis. We show that Nodal signaling triggers explant elongation by inducing mesendodermal progenitors but also suppressing BMP signaling activity at the site of mesendoderm induction. Consistent with this, ectopic BMP signaling in the mesendoderm blocks cell alignment and oriented mesendoderm intercalations, key processes during explant elongation. Translating these ex vivo observations to the intact embryo showed that, similar to explants, Nodal signaling suppresses the effect of BMP signaling on cell intercalations in the dorsal domain, thus allowing robust embryonic axis elongation. These findings suggest a dual function of Nodal signaling in embryonic axis elongation by both inducing mesendoderm and suppressing BMP effects in the dorsal portion of the mesendoderm."}],"publication_identifier":{"eissn":["1477-9129"],"issn":["0950-1991"]},"citation":{"apa":"Schauer, A., Pranjic-Ferscha, K., Hauschild, R., &#38; Heisenberg, C.-P. J. (2024). Robust axis elongation by Nodal-dependent restriction of BMP signaling. <i>Development</i>. Company of Biologists. <a href=\"https://doi.org/10.1242/dev.202316\">https://doi.org/10.1242/dev.202316</a>","mla":"Schauer, Alexandra, et al. “Robust Axis Elongation by Nodal-Dependent Restriction of BMP Signaling.” <i>Development</i>, vol. 151, no. 4, Company of Biologists, 2024, pp. 1–18, doi:<a href=\"https://doi.org/10.1242/dev.202316\">10.1242/dev.202316</a>.","ista":"Schauer A, Pranjic-Ferscha K, Hauschild R, Heisenberg C-PJ. 2024. Robust axis elongation by Nodal-dependent restriction of BMP signaling. Development. 151(4), 1–18.","ieee":"A. Schauer, K. Pranjic-Ferscha, R. Hauschild, and C.-P. J. Heisenberg, “Robust axis elongation by Nodal-dependent restriction of BMP signaling,” <i>Development</i>, vol. 151, no. 4. Company of Biologists, pp. 1–18, 2024.","ama":"Schauer A, Pranjic-Ferscha K, Hauschild R, Heisenberg C-PJ. Robust axis elongation by Nodal-dependent restriction of BMP signaling. <i>Development</i>. 2024;151(4):1-18. doi:<a href=\"https://doi.org/10.1242/dev.202316\">10.1242/dev.202316</a>","short":"A. Schauer, K. Pranjic-Ferscha, R. Hauschild, C.-P.J. Heisenberg, Development 151 (2024) 1–18.","chicago":"Schauer, Alexandra, Kornelija Pranjic-Ferscha, Robert Hauschild, and Carl-Philipp J Heisenberg. “Robust Axis Elongation by Nodal-Dependent Restriction of BMP Signaling.” <i>Development</i>. Company of Biologists, 2024. <a href=\"https://doi.org/10.1242/dev.202316\">https://doi.org/10.1242/dev.202316</a>."},"file_date_updated":"2024-03-04T07:24:43Z","doi":"10.1242/dev.202316","article_processing_charge":"Yes (via OA deal)","department":[{"_id":"CaHe"},{"_id":"Bio"}],"has_accepted_license":"1","corr_author":"1","external_id":{"pmid":["38372390"],"isi":["001170580200001"]},"acknowledgement":"We thank Patrick Müller for sharing the chordintt250 mutant zebrafish line as well as the plasmid for chrd-GFP, Katherine Rogers for sharing the bmp2b plasmid and Andrea Pauli for sharing the draculin plasmid. Diana Pinheiro generated the MZlefty1,2;Tg(sebox::EGFP) line. We are grateful to Patrick Müller, Diana Pinheiro and Katherine Rogers and members of the Heisenberg lab for discussions, technical advice and feedback on the manuscript. We also thank Anna Kicheva and Edouard Hannezo for discussions. We thank the Imaging and Optics Facility as well as the Life Science facility at IST Austria for support with microscopy and fish maintenance.\r\nThis work was supported by a European Research Council Advanced Grant\r\n(MECSPEC 742573 to C.-P.H.). A.S. is a recipient of a DOC Fellowship of the Austrian\r\nAcademy of Sciences at IST Austria. Open Access funding provided by Institute of\r\nScience and Technology Austria. ","date_updated":"2026-10-01T08:32:34Z","ddc":["570"],"_id":"15048","publisher":"Company of Biologists","title":"Robust axis elongation by Nodal-dependent restriction of BMP signaling","oa_version":"Published Version","scopus_import":"1","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","language":[{"iso":"eng"}],"month":"02","project":[{"call_identifier":"H2020","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","_id":"260F1432-B435-11E9-9278-68D0E5697425","grant_number":"742573"},{"_id":"26B1E39C-B435-11E9-9278-68D0E5697425","name":"Mesendoderm specification in zebrafish: The role of extraembryonic tissues","grant_number":"25239"}],"dataavailabilitystatement":"A custom MATLAB script for analyzing cell dispersal has been deposited in the ISTA library (doi:10.15479/AT:ISTA:14926)"},{"type":"software","year":"2024","ddc":["570"],"date_updated":"2026-10-01T08:32:33Z","status":"public","publisher":"Institute of Science and Technology Austria","_id":"14926","related_material":{"record":[{"relation":"used_in_publication","id":"15048","status":"public"}]},"date_published":"2024-02-02T00:00:00Z","title":"Matlab script for analysis of clone dispersal","oa":1,"date_created":"2024-02-02T14:42:26Z","tmp":{"legal_code_url":"https://opensource.org/licenses/MIT","name":"The MIT License","short":"MIT"},"doi":"10.15479/AT:ISTA:14926","file_date_updated":"2024-02-02T14:40:31Z","citation":{"ista":"Hauschild R. 2024. Matlab script for analysis of clone dispersal, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:14926\">10.15479/AT:ISTA:14926</a>.","ieee":"R. Hauschild, “Matlab script for analysis of clone dispersal.” Institute of Science and Technology Austria, 2024.","ama":"Hauschild R. Matlab script for analysis of clone dispersal. 2024. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:14926\">10.15479/AT:ISTA:14926</a>","short":"R. Hauschild, (2024).","chicago":"Hauschild, Robert. “Matlab Script for Analysis of Clone Dispersal.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/AT:ISTA:14926\">https://doi.org/10.15479/AT:ISTA:14926</a>.","apa":"Hauschild, R. (2024). Matlab script for analysis of clone dispersal. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:14926\">https://doi.org/10.15479/AT:ISTA:14926</a>","mla":"Hauschild, Robert. <i>Matlab Script for Analysis of Clone Dispersal</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:14926\">10.15479/AT:ISTA:14926</a>."},"fulldoi":"https://doi.org/10.15479/AT:ISTA:14926","department":[{"_id":"Bio"}],"has_accepted_license":"1","corr_author":"1","file":[{"checksum":"df7f358ae19a176cf710c0a802ce31b1","date_updated":"2024-02-02T14:40:31Z","relation":"main_file","file_name":"README.md","access_level":"open_access","date_created":"2024-02-02T14:40:31Z","creator":"rhauschild","file_size":736,"success":1,"file_id":"14927","content_type":"application/octet-stream"},{"checksum":"10194cc11619eccd8f4b24472e465b7f","date_updated":"2024-02-02T14:40:31Z","relation":"main_file","access_level":"open_access","date_created":"2024-02-02T14:40:31Z","file_name":"Supplementary_file_1.zip","file_size":3543,"creator":"rhauschild","content_type":"application/x-zip-compressed","file_id":"14928","success":1}],"license":"https://opensource.org/licenses/MIT","day":"02","month":"02","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","first_name":"Robert"}]},{"article_number":"7511","dataavailabilitystatement":"Strains generated in this study are available from the corresponding authors upon request. For cryo-EM model building, published pre-60S models PDB-6EM3, PDB-6EM4, PDB-6C0F, PDB-6EM1 and PDB-8V87 were used. Motion-corrected micrographs with annotated particle locations were deposited in EMPIAR with the accession number EMPIAR-12237. The cryo-EM maps of clusters 1 to 4 with the combined datasets were deposited in the EMDB with the accession numbers EMD-51122, EMD-51126, EMD-51128, and EMD-51129. The reconstructions for the treated dataset were deposited with the accession numbers EMD-51175, EMD-51176, EMD-51177, and EMD-51178, while the untreated reconstructions of reported clusters can be found via EMD-51164, EMD-51165, EMD-51166, EMD-51167. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE101 partner repository with the dataset identifier PXD046691. Source data are provided with this paper.","scopus_import":"1","language":[{"iso":"eng"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","month":"08","oa_version":"Published Version","title":"The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S maturation","acknowledgement":"We thank Michael A. McAlear, Micheline Fromont-Racin, Philipp Milkereit, Arlen W. Johnson, Sabine Rospert, Ed Hurt, C. Yam, Günter Daum, Wolfgang Zachariae, Katrin Karbstein, Juan P. G. Ballesta, Mercedes Dosil, Miguel Remacha und Jesus de la Cruz for sharing strains or providing antibodies. We thank the members of the Bergler lab and the Haselbach lab for their helpful discussion. We thank Ellen Zhong for helpful discussions about the quantitative cryoDRGN analysis. This research was supported by the Scientific Service Units of IST Austria through resources provided by the Electron Microscopy Facility. This research was funded in whole, or in part, by the Austrian Science Foundation grants [https://doi.org/10.55776/P32977], [https://doi.org/10.55776/P29451] and [https://doi.org/10.55776/P32536] (to H.B.). Research at the IMP is generously supported by Boehringer Ingelheim and the Austrian Research Promotion Agency (Headquarter grant FFG-852936). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.","external_id":{"pmid":["39209816"],"isi":["001457895200001"]},"_id":"17885","publisher":"Springer Nature","ddc":["570"],"date_updated":"2026-10-01T11:05:46Z","has_accepted_license":"1","department":[{"_id":"EM-Fac"}],"file_date_updated":"2024-09-09T08:56:12Z","doi":"10.1038/s41467-024-51754-3","citation":{"ista":"Kofler L, Grundmann L, Gerhalter M, Prattes M, Merl-Pham J, Zisser G, Grishkovskaya I, Hodirnau V-V, Vareka M, Breinbauer R, Hauck SM, Haselbach D, Bergler H. 2024. The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S maturation. Nature Communications. 15, 7511.","ieee":"L. Kofler <i>et al.</i>, “The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S maturation,” <i>Nature Communications</i>, vol. 15. Springer Nature, 2024.","ama":"Kofler L, Grundmann L, Gerhalter M, et al. The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S maturation. <i>Nature Communications</i>. 2024;15. doi:<a href=\"https://doi.org/10.1038/s41467-024-51754-3\">10.1038/s41467-024-51754-3</a>","short":"L. Kofler, L. Grundmann, M. Gerhalter, M. Prattes, J. Merl-Pham, G. Zisser, I. Grishkovskaya, V.-V. Hodirnau, M. Vareka, R. Breinbauer, S.M. Hauck, D. Haselbach, H. Bergler, Nature Communications 15 (2024).","chicago":"Kofler, Lisa, Lorenz Grundmann, Magdalena Gerhalter, Michael Prattes, Juliane Merl-Pham, Gertrude Zisser, Irina Grishkovskaya, et al. “The Novel Ribosome Biogenesis Inhibitor Usnic Acid Blocks Nucleolar Pre-60S Maturation.” <i>Nature Communications</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41467-024-51754-3\">https://doi.org/10.1038/s41467-024-51754-3</a>.","apa":"Kofler, L., Grundmann, L., Gerhalter, M., Prattes, M., Merl-Pham, J., Zisser, G., … Bergler, H. (2024). The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S maturation. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-024-51754-3\">https://doi.org/10.1038/s41467-024-51754-3</a>","mla":"Kofler, Lisa, et al. “The Novel Ribosome Biogenesis Inhibitor Usnic Acid Blocks Nucleolar Pre-60S Maturation.” <i>Nature Communications</i>, vol. 15, 7511, Springer Nature, 2024, doi:<a href=\"https://doi.org/10.1038/s41467-024-51754-3\">10.1038/s41467-024-51754-3</a>."},"abstract":[{"text":"The formation of new ribosomes is tightly coordinated with cell growth and proliferation. In eukaryotes, the correct assembly of all ribosomal proteins and RNAs follows an intricate scheme of maturation and rearrangement steps across three cellular compartments: the nucleolus, nucleoplasm, and cytoplasm. We demonstrate that usnic acid, a lichen secondary metabolite, inhibits the maturation of the large ribosomal subunit in yeast. We combine biochemical characterization of pre-ribosomal particles with a quantitative single-particle cryo-EM approach to monitor changes in nucleolar particle populations upon drug treatment. Usnic acid rapidly blocks the transition from nucleolar state B to C of Nsa1-associated pre-ribosomes, depleting key maturation factors such as Dbp10 and hindering pre-rRNA processing. This primary nucleolar block rapidly rebounds on earlier stages of the pathway which highlights the regulatory linkages between different steps. In summary, we provide an in-depth characterization of the effect of usnic acid on ribosome biogenesis, which may have implications for its reported anti-cancer activities.","lang":"eng"}],"publication_identifier":{"eissn":["2041-1723"]},"DOAJ_listed":"1","article_processing_charge":"Yes","volume":15,"supplementarymaterial":"yes","quality_controlled":"1","file":[{"content_type":"application/pdf","file_id":"17946","success":1,"file_size":3735024,"creator":"dernst","date_created":"2024-09-09T08:56:12Z","access_level":"open_access","file_name":"2024_NatureComm_Kofler.pdf","date_updated":"2024-09-09T08:56:12Z","relation":"main_file","checksum":"7c044538a47182c826d1b526c52958a2"}],"OA_type":"gold","article_type":"original","pmid":1,"acknowledged_ssus":[{"_id":"EM-Fac"}],"day":"29","author":[{"first_name":"Lisa","full_name":"Kofler, Lisa","last_name":"Kofler"},{"last_name":"Grundmann","full_name":"Grundmann, Lorenz","first_name":"Lorenz"},{"last_name":"Gerhalter","full_name":"Gerhalter, Magdalena","first_name":"Magdalena"},{"last_name":"Prattes","full_name":"Prattes, Michael","first_name":"Michael"},{"first_name":"Juliane","full_name":"Merl-Pham, Juliane","last_name":"Merl-Pham"},{"first_name":"Gertrude","full_name":"Zisser, Gertrude","last_name":"Zisser"},{"full_name":"Grishkovskaya, Irina","first_name":"Irina","last_name":"Grishkovskaya"},{"first_name":"Victor-Valentin","full_name":"Hodirnau, Victor-Valentin","last_name":"Hodirnau","orcid":"0000-0003-3904-947X","id":"3661B498-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Vareka, Martin","first_name":"Martin","last_name":"Vareka"},{"last_name":"Breinbauer","full_name":"Breinbauer, Rolf","first_name":"Rolf"},{"first_name":"Stefanie M.","full_name":"Hauck, Stefanie M.","last_name":"Hauck"},{"full_name":"Haselbach, David","first_name":"David","last_name":"Haselbach"},{"last_name":"Bergler","first_name":"Helmut","full_name":"Bergler, Helmut"}],"isi":1,"das_tickbox":"1","OA_place":"publisher","oa":1,"date_published":"2024-08-29T00:00:00Z","date_created":"2024-09-08T22:01:10Z","type":"journal_article","intvolume":"        15","status":"public","researchdata_availability":"yes","year":"2024","publication":"Nature Communications","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publication_status":"published","fulldoi":"https://doi.org/10.1038/s41467-024-51754-3"},{"oa_version":"Published Version","month":"07","language":[{"iso":"eng"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","scopus_import":"1","project":[{"grant_number":"747687","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","_id":"260AA4E2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"dataavailabilitystatement":"Imaging and flow cytometry raw data are available on request. scRNA-seq data are accessible at the GEO (GSE261996). Bulk RNA-seq data are accessible at the GEO (GSE185488). Source data are provided with this paper.","article_processing_charge":"Yes (in subscription journal)","file_date_updated":"2024-07-22T06:16:11Z","doi":"10.1038/s41586-024-07671-y","citation":{"chicago":"Gärtner, Florian R, Hellen Ishikawa-Ankerhold, Susanne Stutte, Wenwen Fu, Jutta Weitz, Anne Dueck, Bhavishya Nelakuditi, et al. “Plasmacytoid Dendritic Cells Control Homeostasis of Megakaryopoiesis.” <i>Nature</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41586-024-07671-y\">https://doi.org/10.1038/s41586-024-07671-y</a>.","short":"F.R. Gärtner, H. Ishikawa-Ankerhold, S. Stutte, W. Fu, J. Weitz, A. Dueck, B. Nelakuditi, V. Fumagalli, D. Van Den Heuvel, L. Belz, G. Sobirova, Z. Zhang, A. Titova, A.M. Navarro, K. Pekayvaz, M. Lorenz, L. Von Baumgarten, J. Kranich, T. Straub, B. Popper, V. Zheden, W. Kaufmann, C. Guo, G. Piontek, S. Von Stillfried, P. Boor, M. Colonna, S. Clauß, C. Schulz, T. Brocker, B. Walzog, C. Scheiermann, W.C. Aird, C. Nerlov, K. Stark, T. Petzold, S. Engelhardt, M.K. Sixt, R. Hauschild, M. Rudelius, R.A.J. Oostendorp, M. Iannacone, M. Heinig, S. Massberg, Nature 631 (2024) 645–653.","ama":"Gärtner FR, Ishikawa-Ankerhold H, Stutte S, et al. Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis. <i>Nature</i>. 2024;631:645-653. doi:<a href=\"https://doi.org/10.1038/s41586-024-07671-y\">10.1038/s41586-024-07671-y</a>","ieee":"F. R. Gärtner <i>et al.</i>, “Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis,” <i>Nature</i>, vol. 631. Springer Nature, pp. 645–653, 2024.","ista":"Gärtner FR, Ishikawa-Ankerhold H, Stutte S, Fu W, Weitz J, Dueck A, Nelakuditi B, Fumagalli V, Van Den Heuvel D, Belz L, Sobirova G, Zhang Z, Titova A, Navarro AM, Pekayvaz K, Lorenz M, Von Baumgarten L, Kranich J, Straub T, Popper B, Zheden V, Kaufmann W, Guo C, Piontek G, Von Stillfried S, Boor P, Colonna M, Clauß S, Schulz C, Brocker T, Walzog B, Scheiermann C, Aird WC, Nerlov C, Stark K, Petzold T, Engelhardt S, Sixt MK, Hauschild R, Rudelius M, Oostendorp RAJ, Iannacone M, Heinig M, Massberg S. 2024. Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis. Nature. 631, 645–653.","mla":"Gärtner, Florian R., et al. “Plasmacytoid Dendritic Cells Control Homeostasis of Megakaryopoiesis.” <i>Nature</i>, vol. 631, Springer Nature, 2024, pp. 645–53, doi:<a href=\"https://doi.org/10.1038/s41586-024-07671-y\">10.1038/s41586-024-07671-y</a>.","apa":"Gärtner, F. R., Ishikawa-Ankerhold, H., Stutte, S., Fu, W., Weitz, J., Dueck, A., … Massberg, S. (2024). Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-024-07671-y\">https://doi.org/10.1038/s41586-024-07671-y</a>"},"abstract":[{"text":"Platelet homeostasis is essential for vascular integrity and immune defence1,2. Although the process of platelet formation by fragmenting megakaryocytes (MKs; thrombopoiesis) has been extensively studied, the cellular and molecular mechanisms required to constantly replenish the pool of MKs by their progenitor cells (megakaryopoiesis) remains unclear3,4. Here we use intravital imaging to track the cellular dynamics of megakaryopoiesis over days. We identify plasmacytoid dendritic cells (pDCs) as homeostatic sensors that monitor the bone marrow for apoptotic MKs and deliver IFNα to the MK niche triggering local on-demand proliferation and maturation of MK progenitors. This pDC-dependent feedback loop is crucial for MK and platelet homeostasis at steady state and under stress. pDCs are best known for their ability to function as vigilant detectors of viral infection5. We show that virus-induced activation of pDCs interferes with their function as homeostatic sensors of megakaryopoiesis. Consequently, activation of pDCs by SARS-CoV-2 leads to excessive megakaryopoiesis. Together, we identify a pDC-dependent homeostatic circuit that involves innate immune sensing and demand-adapted release of inflammatory mediators to maintain homeostasis of the megakaryocytic lineage.","lang":"eng"}],"publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"corr_author":"1","has_accepted_license":"1","department":[{"_id":"EM-Fac"},{"_id":"MiSi"},{"_id":"Bio"}],"publisher":"Springer Nature","_id":"17284","date_updated":"2026-10-01T11:17:11Z","ddc":["570"],"acknowledgement":"We thank S. Helmer, N. Blount, E. Raatz and Z. Sisic for technical assistance. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) SFB 1123 (S.M. project B06); SFB 914 (S.M. projects B02 and Z01, H.I.-A. project Z01, S.S. project A06, K.S. project B02, C. Schulz project A10, B.W. project A02, C. Scheiermann project B09); SFB 1054 (T.B. project B03); FOR2033 (F.G., R.A.J.O., S.M.); Individual research grant project ID: 514478744 (F.G.); Heisenberg Programme project ID: 514477451 (F.G.); the DZHK (German Center for Cardiovascular Research) (MHA 1.4VD (S.M.), Postdoc Start-up Grant, 81×3600213 (F.G.)); and LMUexcellence NFF (F.G.). W.F. received funding from China Scholarship Council (CSC, no. 201306270012). P.B. is supported by the German Research Foundation (DFG, project IDs 322900939, 432698239 and 445703531), European Research Council (ERC Consolidator grant no. 101001791) and the Federal Ministry of Education and Research (BMBF, STOP-FSGS-01GM2202C and NATON within the framework of the Network of University Medicine, no. 01KX2121). S.v.S. is supported by the START-Program of the Faculty of Medicine of the RWTH Aachen University (AZ 125/17). A.D. and S.E. are supported by the German Research Foundation (SFB TRR 267); S.E. by the BMBF in the framework of the Cluster4future program (CNATM—Cluster for Nucleic Acid Therapeutics Munich). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 833440 to S.M.). F.G. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 747687. The project is funded by the European Union (ERC, MEKanics, 101078110). Views and opinions expressed are those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them.","external_id":{"pmid":["38987596"],"isi":["001281636500020"]},"title":"Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis","ec_funded":1,"das_tickbox":"1","page":"645-653","author":[{"first_name":"Florian R","full_name":"Gärtner, Florian R","last_name":"Gärtner","orcid":"0000-0001-6120-3723","id":"397A88EE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Ishikawa-Ankerhold, Hellen","first_name":"Hellen","last_name":"Ishikawa-Ankerhold"},{"full_name":"Stutte, Susanne","first_name":"Susanne","last_name":"Stutte"},{"last_name":"Fu","full_name":"Fu, Wenwen","first_name":"Wenwen"},{"last_name":"Weitz","full_name":"Weitz, Jutta","first_name":"Jutta"},{"last_name":"Dueck","full_name":"Dueck, Anne","first_name":"Anne"},{"last_name":"Nelakuditi","full_name":"Nelakuditi, Bhavishya","first_name":"Bhavishya"},{"full_name":"Fumagalli, Valeria","first_name":"Valeria","last_name":"Fumagalli"},{"last_name":"Van Den Heuvel","first_name":"Dominic","full_name":"Van Den Heuvel, Dominic"},{"last_name":"Belz","full_name":"Belz, Larissa","first_name":"Larissa"},{"last_name":"Sobirova","full_name":"Sobirova, Gulnoza","first_name":"Gulnoza"},{"full_name":"Zhang, Zhe","first_name":"Zhe","last_name":"Zhang"},{"full_name":"Titova, Anna","first_name":"Anna","last_name":"Titova"},{"full_name":"Navarro, Alejandro Martinez","first_name":"Alejandro Martinez","last_name":"Navarro"},{"last_name":"Pekayvaz","first_name":"Kami","full_name":"Pekayvaz, Kami"},{"last_name":"Lorenz","full_name":"Lorenz, Michael","first_name":"Michael"},{"last_name":"Von Baumgarten","first_name":"Louisa","full_name":"Von Baumgarten, Louisa"},{"first_name":"Jan","full_name":"Kranich, Jan","last_name":"Kranich"},{"last_name":"Straub","full_name":"Straub, Tobias","first_name":"Tobias"},{"full_name":"Popper, Bastian","first_name":"Bastian","last_name":"Popper"},{"id":"39C5A68A-F248-11E8-B48F-1D18A9856A87","last_name":"Zheden","orcid":"0000-0002-9438-4783","full_name":"Zheden, Vanessa","first_name":"Vanessa"},{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","last_name":"Kaufmann","orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter","first_name":"Walter"},{"full_name":"Guo, Chenglong","first_name":"Chenglong","last_name":"Guo"},{"last_name":"Piontek","full_name":"Piontek, Guido","first_name":"Guido"},{"last_name":"Von Stillfried","first_name":"Saskia","full_name":"Von Stillfried, Saskia"},{"full_name":"Boor, Peter","first_name":"Peter","last_name":"Boor"},{"full_name":"Colonna, Marco","first_name":"Marco","last_name":"Colonna"},{"last_name":"Clauß","full_name":"Clauß, Sebastian","first_name":"Sebastian"},{"first_name":"Christian","full_name":"Schulz, Christian","last_name":"Schulz"},{"full_name":"Brocker, Thomas","first_name":"Thomas","last_name":"Brocker"},{"last_name":"Walzog","first_name":"Barbara","full_name":"Walzog, Barbara"},{"last_name":"Scheiermann","first_name":"Christoph","full_name":"Scheiermann, Christoph"},{"full_name":"Aird, William C.","first_name":"William C.","last_name":"Aird"},{"last_name":"Nerlov","full_name":"Nerlov, Claus","first_name":"Claus"},{"full_name":"Stark, Konstantin","first_name":"Konstantin","last_name":"Stark"},{"first_name":"Tobias","full_name":"Petzold, Tobias","last_name":"Petzold"},{"last_name":"Engelhardt","first_name":"Stefan","full_name":"Engelhardt, Stefan"},{"full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179"},{"id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","last_name":"Hauschild","full_name":"Hauschild, Robert","first_name":"Robert"},{"last_name":"Rudelius","full_name":"Rudelius, Martina","first_name":"Martina"},{"full_name":"Oostendorp, Robert A.J.","first_name":"Robert A.J.","last_name":"Oostendorp"},{"last_name":"Iannacone","full_name":"Iannacone, Matteo","first_name":"Matteo"},{"last_name":"Heinig","first_name":"Matthias","full_name":"Heinig, Matthias"},{"last_name":"Massberg","full_name":"Massberg, Steffen","first_name":"Steffen"}],"isi":1,"day":"18","article_type":"original","pmid":1,"quality_controlled":"1","file":[{"checksum":"aa004afc72d2489f0fb0fcbc9919fbbd","date_updated":"2024-07-22T06:16:11Z","relation":"main_file","file_name":"2024_Nature_Gaertner.pdf","access_level":"open_access","date_created":"2024-07-22T06:16:11Z","creator":"dernst","file_size":15704819,"success":1,"content_type":"application/pdf","file_id":"17286"}],"volume":631,"supplementarymaterial":"yes","publication_status":"published","fulldoi":"https://doi.org/10.1038/s41586-024-07671-y","publication":"Nature","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"related_material":{"link":[{"relation":"software","url":"https://github.com/heiniglab/gaertner_megakaryocytes"}]},"intvolume":"       631","status":"public","year":"2024","researchdata_availability":"upon request","type":"journal_article","date_created":"2024-07-21T22:01:02Z","oa":1,"date_published":"2024-07-18T00:00:00Z"},{"year":"2024","status":"public","researchdata_availability":"yes","related_material":{"record":[{"status":"public","id":"23025","relation":"research_data"}],"link":[{"url":" https://github.com/fuzikt/tomostarpy.","relation":"software"}]},"intvolume":"        10","type":"journal_article","issue":"15","date_created":"2025-01-27T14:32:34Z","date_published":"2024-04-01T00:00:00Z","oa":1,"fulldoi":"https://doi.org/10.1126/sciadv.adk1954","publication_status":"published","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publication":"Science Advances","pmid":1,"article_type":"original","OA_type":"gold","file":[{"file_name":"2024_ScienceAdv_Homola.pdf","date_created":"2025-01-27T14:40:08Z","access_level":"open_access","relation":"main_file","date_updated":"2025-01-27T14:40:08Z","checksum":"291dd7ceccbe6bfd8e0a9157584f88e9","success":1,"content_type":"application/pdf","file_id":"18921","creator":"dernst","file_size":40623405}],"quality_controlled":"1","supplementarymaterial":"yes","volume":10,"OA_place":"publisher","das_tickbox":"1","author":[{"full_name":"Homola, Miroslav","first_name":"Miroslav","last_name":"Homola"},{"first_name":"Renate Carina","full_name":"Büttner, Renate Carina","id":"3b7984c9-17ff-11ed-b6fe-f943c4a5b626","last_name":"Büttner"},{"last_name":"Füzik","full_name":"Füzik, Tibor","first_name":"Tibor"},{"last_name":"Křepelka","first_name":"Pavel","full_name":"Křepelka, Pavel"},{"full_name":"Holbová, Radka","first_name":"Radka","last_name":"Holbová"},{"last_name":"Nováček","first_name":"Jiří","full_name":"Nováček, Jiří"},{"last_name":"Chaillet","first_name":"Marten L.","full_name":"Chaillet, Marten L."},{"full_name":"Žák, Jakub","first_name":"Jakub","last_name":"Žák"},{"first_name":"Danyil","full_name":"Grybchuk, Danyil","last_name":"Grybchuk"},{"last_name":"Förster","full_name":"Förster, Friedrich","first_name":"Friedrich"},{"full_name":"Wilson, William H.","first_name":"William H.","last_name":"Wilson"},{"last_name":"Schroeder","full_name":"Schroeder, Declan C.","first_name":"Declan C."},{"last_name":"Plevka","first_name":"Pavel","full_name":"Plevka, Pavel"}],"day":"01","ddc":["570"],"date_updated":"2026-10-01T11:15:30Z","publisher":"American Association for the Advancement of Science","_id":"18920","external_id":{"pmid":["38598627"]},"acknowledgement":"We acknowledge (i) the Cryo-Electron Microscopy and Tomography Core Facility and Proteomics Core Facility of the Central European Institute of Technology (CEITEC), Masaryk University, supported by the Ministry of Education, Youth, and Sports of the Czech Republic (grant LM2018127); (ii) the Cellular Imaging Core Facility supported by the Czech-BioImaging large RI project (LM2018129 funded by MEYS CR); and (iii) Plant Sciences Core Facility for support with obtaining scientific data presented here. We acknowledge support from the project National Institute of Virology and Bacteriology (Program EXCELES, ID project no. LX22NPO5103), funded by the European Union - Next Generation EU. This work received funding from the Czech Science Foundation grant GX 19-259882X to P.P., from European Regional Development Fund-Project “MSCAfellow2@MUNI” (no. CZ.02.2.69/0.0/0.0/18_070/0009846) to C.R.B., and from Brno PhD talent scholarship funded by Brno city municipality to M.H.","title":"Structure and replication cycle of a virus infecting climate-modulating alga Emiliania huxleyi","article_processing_charge":"Yes","DOAJ_listed":"1","abstract":[{"text":"The globally distributed marine alga Emiliania huxleyi has cooling effect on the Earth’s climate. The population density of E. huxleyi is restricted by Nucleocytoviricota viruses, including E. huxleyi virus 201 (EhV-201). Despite the impact of E. huxleyi viruses on the climate, there is limited information about their structure and replication. Here, we show that the dsDNA genome inside the EhV-201 virion is protected by an inner membrane, capsid, and outer membrane. EhV-201 virions infect E. huxleyi by using fivefold vertices to bind to and fuse the virus’ inner membrane with the cell plasma membrane. Progeny virions assemble in the cytoplasm at the surface of endoplasmic reticulum–derived membrane segments. Genome packaging initiates synchronously with the capsid assembly and completes through an aperture in the forming capsid. The genome-filled capsids acquire an outer membrane by budding into intracellular vesicles. EhV-201 infection induces a loss of surface protective layers from E. huxleyi cells, which enables the continuous release of virions by exocytosis.","lang":"eng"}],"publication_identifier":{"eissn":["2375-2548"]},"doi":"10.1126/sciadv.adk1954","file_date_updated":"2025-01-27T14:40:08Z","citation":{"ista":"Homola M, Büttner RC, Füzik T, Křepelka P, Holbová R, Nováček J, Chaillet ML, Žák J, Grybchuk D, Förster F, Wilson WH, Schroeder DC, Plevka P. 2024. Structure and replication cycle of a virus infecting climate-modulating alga Emiliania huxleyi. Science Advances. 10(15), eadk1954.","ieee":"M. Homola <i>et al.</i>, “Structure and replication cycle of a virus infecting climate-modulating alga Emiliania huxleyi,” <i>Science Advances</i>, vol. 10, no. 15. American Association for the Advancement of Science, 2024.","ama":"Homola M, Büttner RC, Füzik T, et al. Structure and replication cycle of a virus infecting climate-modulating alga Emiliania huxleyi. <i>Science Advances</i>. 2024;10(15). doi:<a href=\"https://doi.org/10.1126/sciadv.adk1954\">10.1126/sciadv.adk1954</a>","short":"M. Homola, R.C. Büttner, T. Füzik, P. Křepelka, R. Holbová, J. Nováček, M.L. Chaillet, J. Žák, D. Grybchuk, F. Förster, W.H. Wilson, D.C. Schroeder, P. Plevka, Science Advances 10 (2024).","chicago":"Homola, Miroslav, Renate Carina Büttner, Tibor Füzik, Pavel Křepelka, Radka Holbová, Jiří Nováček, Marten L. Chaillet, et al. “Structure and Replication Cycle of a Virus Infecting Climate-Modulating Alga Emiliania Huxleyi.” <i>Science Advances</i>. American Association for the Advancement of Science, 2024. <a href=\"https://doi.org/10.1126/sciadv.adk1954\">https://doi.org/10.1126/sciadv.adk1954</a>.","apa":"Homola, M., Büttner, R. C., Füzik, T., Křepelka, P., Holbová, R., Nováček, J., … Plevka, P. (2024). Structure and replication cycle of a virus infecting climate-modulating alga Emiliania huxleyi. <i>Science Advances</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/sciadv.adk1954\">https://doi.org/10.1126/sciadv.adk1954</a>","mla":"Homola, Miroslav, et al. “Structure and Replication Cycle of a Virus Infecting Climate-Modulating Alga Emiliania Huxleyi.” <i>Science Advances</i>, vol. 10, no. 15, eadk1954, American Association for the Advancement of Science, 2024, doi:<a href=\"https://doi.org/10.1126/sciadv.adk1954\">10.1126/sciadv.adk1954</a>."},"department":[{"_id":"EM-Fac"}],"has_accepted_license":"1","dataavailabilitystatement":"Cryo-EM maps and structure coordinates were deposited to the Electron Microscopy Data Bank (EMDB) and Protein Data Bank (PDB), respectively, with the following accession numbers: (i) EhV-201 virion vertex reconstructed using a single-particle approach and a mask with the diameter of 50 nm (EMD-17650); (ii) EhV-201 virion vertex reconstructed using sub-tomogram averaging and a mask with the diameter of 50 nm (EMD-17649); (iii) EhV-201 virion vertex reconstructed using sub-tomogram averaging and a mask with the diameter of 50 nm and a mask covering only the capsid layer (EMD-19036) and the fitted structure of AlphaFold2 predicted EhV-201 major capsid protein and penton protein (PDB 8RBT); (iv) EhV-201 virion vertex reconstructed by sub-tomogram averaging and a mask with the diameter of 120 nm (EMD-17651); and (v) composite map of the EhV201 virion (EMD-19035) and corresponding structure of icosahedral asymmetric unit (PDB 8RBS). All custom scripts used during tomographic reconstruction have been made available at https://github.com/fuzikt/tomostarpy. Additional files have been made available at https://doi.org/10.5061/dryad.p5hqbzkw0: (i) cryo-ET tilt series of lamellas of control and EhV-201 infected E. huxleyi cells; (ii) segmentations of cryo-tomograms of infected and control cells; (iii) block face imaging data series of high-pressure frozen and resin-embedded E. huxleyi infected by EhV-201; (iv) scripts used during tomographic reconstruction; (v) fluorescence microscopy images of E. huxleyi infected by EhV-201; and (vi) mass spectrometry report of EhV-201 virion protein composition. Cryo-ET tilt series used for EhV-201 virion structure determination were deposited to EMPIAR and linked to the file EMD-17649. All other data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.","article_number":"eadk1954 ","oa_version":"Published Version","month":"04","language":[{"iso":"eng"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","scopus_import":"1"},{"publication":"New Aspects in Analyzing the Synaptic Organization of the Brain","fulldoi":"https://doi.org/10.1007/978-1-0716-4019-7_8","publication_status":"published","type":"book_chapter","year":"2024","status":"public","researchdata_availability":"no","date_published":"2024-08-27T00:00:00Z","date_created":"2024-09-10T12:32:38Z","edition":"1","page":"123-137","das_tickbox":"0","ec_funded":1,"day":"27","acknowledged_ssus":[{"_id":"EM-Fac"}],"author":[{"first_name":"David","full_name":"Kleindienst, David","id":"42E121A4-F248-11E8-B48F-1D18A9856A87","last_name":"Kleindienst"},{"id":"D93824F4-D9BA-11E9-BB12-F207E6697425","last_name":"Costanzo","orcid":"0000-0001-9732-3815","full_name":"Costanzo, Tommaso","first_name":"Tommaso"},{"full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","last_name":"Shigemoto"}],"quality_controlled":"1","editor":[{"last_name":"Lübke","first_name":"Joachim H.R. ","full_name":"Lübke, Joachim H.R. "},{"full_name":"Rollenhagen, Astrid","first_name":"Astrid","last_name":"Rollenhagen"}],"supplementarymaterial":"no","publication_identifier":{"eissn":["1940-6045"],"isbn":["9781071640180"],"eisbn":["9781071640197"],"issn":["0893-2336"]},"abstract":[{"text":"Sodium dodecyl sulfate-digested freeze-fracture replica labeling (SDS-FRL) is an electron microscope (EM) sample preparation technique which allows for high-resolution visualization of membrane proteins with high sensitivity. However, image acquisition of specific replica profiles such as synapses in a large field of EM view needs a valid experience and a long time for manual searching. Here, we describe how to utilize deep learning for automatizing image acquisition of specific profiles of interest in replica samples. This protocol facilitates the labor-intensive collection of EM images, in particular for rare profiles. We provide instructions for using SerialEM image acquisition software in conjunction with object detection by our newly developed deep learning software DarEM, to automatically acquire tilt series of all synapses in a selected region. We then show how to perform a mostly automated analysis of gold particle labeling in the acquired images by utilizing Darea software.","lang":"eng"}],"citation":{"mla":"Kleindienst, David, et al. “Automated Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep Learning.” <i>New Aspects in Analyzing the Synaptic Organization of the Brain</i>, edited by Joachim H.R.  Lübke and Astrid Rollenhagen, 1st ed., Springer Nature, 2024, pp. 123–37, doi:<a href=\"https://doi.org/10.1007/978-1-0716-4019-7_8\">10.1007/978-1-0716-4019-7_8</a>.","apa":"Kleindienst, D., Costanzo, T., &#38; Shigemoto, R. (2024). Automated Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep Learning. In J. H. R. Lübke &#38; A. Rollenhagen (Eds.), <i>New Aspects in Analyzing the Synaptic Organization of the Brain</i> (1st ed., pp. 123–137). New York: Springer Nature. <a href=\"https://doi.org/10.1007/978-1-0716-4019-7_8\">https://doi.org/10.1007/978-1-0716-4019-7_8</a>","ieee":"D. Kleindienst, T. Costanzo, and R. Shigemoto, “Automated Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep Learning,” in <i>New Aspects in Analyzing the Synaptic Organization of the Brain</i>, 1st ed., J. H. R. Lübke and A. Rollenhagen, Eds. New York: Springer Nature, 2024, pp. 123–137.","ista":"Kleindienst D, Costanzo T, Shigemoto R. 2024.Automated Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep Learning. In: New Aspects in Analyzing the Synaptic Organization of the Brain. Neuromethods, , 123–137.","short":"D. Kleindienst, T. Costanzo, R. Shigemoto, in:, J.H.R. Lübke, A. Rollenhagen (Eds.), New Aspects in Analyzing the Synaptic Organization of the Brain, 1st ed., Springer Nature, New York, 2024, pp. 123–137.","chicago":"Kleindienst, David, Tommaso Costanzo, and Ryuichi Shigemoto. “Automated Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep Learning.” In <i>New Aspects in Analyzing the Synaptic Organization of the Brain</i>, edited by Joachim H.R.  Lübke and Astrid Rollenhagen, 1st ed., 123–37. New York: Springer Nature, 2024. <a href=\"https://doi.org/10.1007/978-1-0716-4019-7_8\">https://doi.org/10.1007/978-1-0716-4019-7_8</a>.","ama":"Kleindienst D, Costanzo T, Shigemoto R. Automated Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep Learning. In: Lübke JHR, Rollenhagen A, eds. <i>New Aspects in Analyzing the Synaptic Organization of the Brain</i>. 1st ed. New York: Springer Nature; 2024:123-137. doi:<a href=\"https://doi.org/10.1007/978-1-0716-4019-7_8\">10.1007/978-1-0716-4019-7_8</a>"},"doi":"10.1007/978-1-0716-4019-7_8","article_processing_charge":"No","department":[{"_id":"EM-Fac"},{"_id":"RySh"}],"alternative_title":["Neuromethods"],"corr_author":"1","place":"New York","acknowledgement":"This research was supported by the European Research Council Advanced Grant 694539 to RS and by the Scientific Service Units of IST Austria through resources provided by the Electron Microscopy Facility.","date_updated":"2026-10-01T11:17:28Z","_id":"18052","publisher":"Springer Nature","title":"Automated Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep Learning","oa_version":"None","scopus_import":"1","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","language":[{"iso":"eng"}],"month":"08","project":[{"_id":"25CA28EA-B435-11E9-9278-68D0E5697425","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","call_identifier":"H2020","grant_number":"694539"}]},{"OA_type":"green","oa_version":"None","OA_place":"repository","main_file_link":[{"url":"https://doi.org/10.5061/dryad.p5hqbzkw0","open_access":"1"}],"day":"07","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","month":"02","author":[{"full_name":"Homola, Miroslav","first_name":"Miroslav","last_name":"Homola"},{"full_name":"Büttner, Carina","first_name":"Carina","last_name":"Büttner"},{"last_name":"Füzik","first_name":"Tibor","full_name":"Füzik, Tibor"},{"last_name":"Krepelka","full_name":"Krepelka, Pavel","first_name":"Pavel"},{"last_name":"Holbová","first_name":"Radka","full_name":"Holbová, Radka"},{"first_name":"Marten","full_name":"Chaillet, Marten","last_name":"Chaillet"},{"last_name":"Nováček","first_name":"Jiří","full_name":"Nováček, Jiří"},{"first_name":"Friedrich","full_name":"Förster, Friedrich","last_name":"Förster"},{"full_name":"Wilson, William","first_name":"William","last_name":"Wilson"},{"first_name":"Declan","full_name":"Schroeder, Declan","last_name":"Schroeder"},{"full_name":"Plevka, Pavel","first_name":"Pavel","last_name":"Plevka"}],"type":"research_data_reference","date_updated":"2026-10-01T11:15:29Z","ddc":["570"],"status":"public","year":"2024","_id":"23025","related_material":{"record":[{"id":"18920","status":"public","relation":"used_in_publication"}]},"publisher":"Dryad","date_published":"2024-02-07T00:00:00Z","title":"Data: Structure and replication cycle of a virus infecting climate-modulating alga Emiliania huxleyi","oa":1,"date_created":"2026-10-01T11:13:02Z","abstract":[{"text":"The globally distributed marine alga Emiliania huxleyi produces reflective calcite disks (coccoliths) that increase the albedo of ocean water and thus reduce the heat absorption in the ocean, which cools the Earth’s climate. The population density of E. huxleyi is restricted by Nucleocytoviricota viruses, including E. huxleyi virus 201 (EhV-201). Despite the impact of E. huxleyi viruses on the climate, there is limited information about their structure and replication. Here we show that the dsDNA genome inside the EhV-201 virion is protected by an inner membrane, capsid, and outer membrane decorated with numerous transmembrane proteins. The virions are prone to deformation, and parts of their capsids deviate from the icosahedral arrangement. EhV-201 virions infect E. huxleyi by using their fivefold vertex to bind to a host cell and fuse the virus’s inner membrane with the plasma membrane. Whereas the replication of EhV-201 probably occurs in the nucleus, virions assemble in the cytoplasm at the surface of endoplasmic reticulum-derived membrane segments. Genome packaging initiates synchronously with the capsid assembly and completes through an aperture in the forming capsid. Upon the completion of genome packaging, the capsids change conformation, which enables them to acquire an outer membrane by budding into intracellular vesicles. EhV-201 infection induces a loss of surface protective layers from E. huxleyi cells, which allows the continuous release of virions by exocytosis. Our results provide insight into how EhVs bypass the surface protective layers of E. huxleyi and exploit the organelles of an infected cell for progeny assembly.","lang":"eng"}],"doi":"10.5061/dryad.p5hqbzkw0","citation":{"mla":"Homola, Miroslav, et al. <i>Data: Structure and Replication Cycle of a Virus Infecting Climate-Modulating Alga Emiliania Huxleyi</i>. Dryad, 2024, doi:<a href=\"https://doi.org/10.5061/dryad.p5hqbzkw0\">10.5061/dryad.p5hqbzkw0</a>.","apa":"Homola, M., Büttner, C., Füzik, T., Krepelka, P., Holbová, R., Chaillet, M., … Plevka, P. (2024). Data: Structure and replication cycle of a virus infecting climate-modulating alga Emiliania huxleyi. Dryad. <a href=\"https://doi.org/10.5061/dryad.p5hqbzkw0\">https://doi.org/10.5061/dryad.p5hqbzkw0</a>","short":"M. Homola, C. Büttner, T. Füzik, P. Krepelka, R. Holbová, M. Chaillet, J. Nováček, F. Förster, W. Wilson, D. Schroeder, P. Plevka, (2024).","chicago":"Homola, Miroslav, Carina Büttner, Tibor Füzik, Pavel Krepelka, Radka Holbová, Marten Chaillet, Jiří Nováček, et al. “Data: Structure and Replication Cycle of a Virus Infecting Climate-Modulating Alga Emiliania Huxleyi.” Dryad, 2024. <a href=\"https://doi.org/10.5061/dryad.p5hqbzkw0\">https://doi.org/10.5061/dryad.p5hqbzkw0</a>.","ama":"Homola M, Büttner C, Füzik T, et al. Data: Structure and replication cycle of a virus infecting climate-modulating alga Emiliania huxleyi. 2024. doi:<a href=\"https://doi.org/10.5061/dryad.p5hqbzkw0\">10.5061/dryad.p5hqbzkw0</a>","ieee":"M. Homola <i>et al.</i>, “Data: Structure and replication cycle of a virus infecting climate-modulating alga Emiliania huxleyi.” Dryad, 2024.","ista":"Homola M, Büttner C, Füzik T, Krepelka P, Holbová R, Chaillet M, Nováček J, Förster F, Wilson W, Schroeder D, Plevka P. 2024. Data: Structure and replication cycle of a virus infecting climate-modulating alga Emiliania huxleyi, Dryad, <a href=\"https://doi.org/10.5061/dryad.p5hqbzkw0\">10.5061/dryad.p5hqbzkw0</a>."},"article_processing_charge":"No","fulldoi":"https://doi.org/10.5061/dryad.p5hqbzkw0","department":[{"_id":"EM-Fac"}]},{"article_type":"original","pmid":1,"quality_controlled":"1","file":[{"file_name":"2024_JCB_Zens.pdf","access_level":"open_access","date_created":"2024-03-25T12:52:04Z","checksum":"90d1984a93660735e506c2a304bc3f73","date_updated":"2024-03-25T12:52:04Z","relation":"main_file","success":1,"file_id":"15188","content_type":"application/pdf","creator":"dernst","file_size":11907016}],"volume":223,"supplementarymaterial":"yes","ec_funded":1,"das_tickbox":"1","author":[{"last_name":"Zens","id":"45FD126C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9561-1239","full_name":"Zens, Bettina","first_name":"Bettina"},{"full_name":"Fäßler, Florian","first_name":"Florian","id":"404F5528-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7149-769X","last_name":"Fäßler"},{"last_name":"Hansen","id":"1063c618-6f9b-11ec-9123-f912fccded63","orcid":"0000-0001-7967-2085","full_name":"Hansen, Jesse","first_name":"Jesse"},{"full_name":"Hauschild, Robert","first_name":"Robert","orcid":"0000-0001-9843-3522","last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Datler","id":"3B12E2E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3616-8580","full_name":"Datler, Julia","first_name":"Julia"},{"last_name":"Hodirnau","orcid":"0000-0003-3904-947X","id":"3661B498-F248-11E8-B48F-1D18A9856A87","first_name":"Victor-Valentin","full_name":"Hodirnau, Victor-Valentin"},{"last_name":"Zheden","id":"39C5A68A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9438-4783","full_name":"Zheden, Vanessa","first_name":"Vanessa"},{"full_name":"Alanko, Jonna H","first_name":"Jonna H","orcid":"0000-0002-7698-3061","last_name":"Alanko","id":"2CC12E8C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Michael K","full_name":"Sixt, Michael K","last_name":"Sixt","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Schur","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4790-8078","full_name":"Schur, Florian KM","first_name":"Florian KM"}],"isi":1,"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"ScienComp"},{"_id":"EM-Fac"},{"_id":"M-Shop"}],"day":"20","intvolume":"       223","researchdata_availability":"yes","status":"public","year":"2024","issue":"6","type":"journal_article","date_created":"2024-03-21T06:45:51Z","oa":1,"date_published":"2024-03-20T00:00:00Z","publication_status":"published","fulldoi":"https://doi.org/10.1083/jcb.202309125","publication":"Journal of Cell Biology","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"project":[{"grant_number":"P33367","name":"Structure and isoform diversity of the Arp2/3 complex","_id":"9B954C5C-BA93-11EA-9121-9846C619BF3A"},{"grant_number":"E435","_id":"7bd318a1-9f16-11ee-852c-cc9217763180","name":"In Situ Actin Structures via Hybrid Cryo-electron Microscopy"},{"call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","name":"Cellular Navigation Along Spatial Gradients","grant_number":"724373"},{"name":"NÖ-Fonds Preis für die Jungforscherin des Jahres am IST Austria","_id":"059B463C-7A3F-11EA-A408-12923DDC885E"},{"_id":"2615199A-B435-11E9-9278-68D0E5697425","name":"Spatiotemporal regulation of chemokine-induced signalling in leukocyte chemotaxis","grant_number":"21317"},{"name":"CryoMinflux-guided in-situ visual proteomics and structure determination","_id":"62909c6f-2b32-11ec-9570-e1476aab5308","grant_number":"CZI01"}],"article_number":"e202309125","dataavailabilitystatement":"Representative tomograms containing the data shown in Fig. 3, and Figs. S5 and S9 have been deposited in the Electron Microscopy Data Bank under accession codes: EMD-18490, EMD-18491, EMD-18492, EMD-18493, and EMD-18494. All tilt series, including frames, raw tilt series, and reconstructed IsoNet-filtered tomograms, were deposited in the Electron Microscopy Public Image Archive database under the accession code EMPIAR-11897.","oa_version":"Published Version","language":[{"iso":"eng"}],"month":"03","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","scopus_import":"1","publisher":"Rockefeller University Press","_id":"15146","ddc":["570"],"date_updated":"2026-10-01T11:24:27Z","acknowledgement":"Open Access funding provided by IST Austria. We thank Armel Nicolas and his team at the ISTA proteomics facility, Alois Schloegl, Stefano Elefante, and colleagues at the ISTA Scientific Computing facility, Tommaso Constanzo and Ludek Lovicar at the Electron Microsocpy Facility (EMF), and Thomas Menner at the Miba Machine shop for their support. We also thank Wanda Kukulski (University of Bern) as well as Darío Porley, Andreas Thader, and other members of the Schur group for helpful discussions. Matt Swulius and Jessica Heebner provided great support in using Dragonfly. We thank Dorotea Fracciolla (Art & Science) for support in figure illustration.\r\n\r\nThis research was supported by the Scientific Service Units of ISTA through resources provided by Scientific Computing, the Lab Support Facility, and the Electron Microscopy Facility. We acknowledge funding support from the following sources: Austrian Science Fund (FWF) grant P33367 (to F.K.M. Schur), the Federation of European Biochemical Societies (to F.K.M. Schur), Niederösterreich (NÖ) Fonds (to B. Zens), FWF grant E435 (to J.M. Hansen), European Research Council under the European Union’s Horizon 2020 research (grant agreement No. 724373) (to M. Sixt), and Jenny and Antti Wihuri Foundation (to J. Alanko). This publication has been made possible in part by CZI grant DAF2021-234754 and grant DOI https://doi.org/10.37921/812628ebpcwg from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation (to F.K.M. Schur).","external_id":{"pmid":["38506714"],"isi":["001264190100001"]},"title":"Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural landscape of extracellular matrix","article_processing_charge":"Yes (via OA deal)","citation":{"ista":"Zens B, Fäßler F, Hansen J, Hauschild R, Datler J, Hodirnau V-V, Zheden V, Alanko JH, Sixt MK, Schur FK. 2024. Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural landscape of extracellular matrix. Journal of Cell Biology. 223(6), e202309125.","ieee":"B. Zens <i>et al.</i>, “Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural landscape of extracellular matrix,” <i>Journal of Cell Biology</i>, vol. 223, no. 6. Rockefeller University Press, 2024.","ama":"Zens B, Fäßler F, Hansen J, et al. Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural landscape of extracellular matrix. <i>Journal of Cell Biology</i>. 2024;223(6). doi:<a href=\"https://doi.org/10.1083/jcb.202309125\">10.1083/jcb.202309125</a>","chicago":"Zens, Bettina, Florian Fäßler, Jesse Hansen, Robert Hauschild, Julia Datler, Victor-Valentin Hodirnau, Vanessa Zheden, Jonna H Alanko, Michael K Sixt, and Florian KM Schur. “Lift-out Cryo-FIBSEM and Cryo-ET Reveal the Ultrastructural Landscape of Extracellular Matrix.” <i>Journal of Cell Biology</i>. Rockefeller University Press, 2024. <a href=\"https://doi.org/10.1083/jcb.202309125\">https://doi.org/10.1083/jcb.202309125</a>.","short":"B. Zens, F. Fäßler, J. Hansen, R. Hauschild, J. Datler, V.-V. Hodirnau, V. Zheden, J.H. Alanko, M.K. Sixt, F.K. Schur, Journal of Cell Biology 223 (2024).","apa":"Zens, B., Fäßler, F., Hansen, J., Hauschild, R., Datler, J., Hodirnau, V.-V., … Schur, F. K. (2024). Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural landscape of extracellular matrix. <i>Journal of Cell Biology</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1083/jcb.202309125\">https://doi.org/10.1083/jcb.202309125</a>","mla":"Zens, Bettina, et al. “Lift-out Cryo-FIBSEM and Cryo-ET Reveal the Ultrastructural Landscape of Extracellular Matrix.” <i>Journal of Cell Biology</i>, vol. 223, no. 6, e202309125, Rockefeller University Press, 2024, doi:<a href=\"https://doi.org/10.1083/jcb.202309125\">10.1083/jcb.202309125</a>."},"file_date_updated":"2024-03-25T12:52:04Z","doi":"10.1083/jcb.202309125","publication_identifier":{"issn":["0021-9525"],"eissn":["1540-8140"]},"abstract":[{"lang":"eng","text":"The extracellular matrix (ECM) serves as a scaffold for cells and plays an essential role in regulating numerous cellular processes, including cell migration and proliferation. Due to limitations in specimen preparation for conventional room-temperature electron microscopy, we lack structural knowledge on how ECM components are secreted, remodeled, and interact with surrounding cells. We have developed a 3D-ECM platform compatible with sample thinning by cryo-focused ion beam milling, the lift-out extraction procedure, and cryo-electron tomography. Our workflow implements cell-derived matrices (CDMs) grown on EM grids, resulting in a versatile tool closely mimicking ECM environments. This allows us to visualize ECM for the first time in its hydrated, native context. Our data reveal an intricate network of extracellular fibers, their positioning relative to matrix-secreting cells, and previously unresolved structural entities. Our workflow and results add to the structural atlas of the ECM, providing novel insights into its secretion and assembly."}],"corr_author":"1","has_accepted_license":"1","department":[{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"Bio"},{"_id":"EM-Fac"}]},{"fulldoi":"https://doi.org/10.1016/j.mssp.2024.108231","publication_status":"published","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publication":"Materials Science in Semiconductor Processing","status":"public","year":"2024","researchdata_availability":"not applicable","intvolume":"       174","type":"journal_article","issue":"5","date_created":"2024-02-22T14:10:40Z","date_published":"2024-05-20T00:00:00Z","oa":1,"OA_place":"publisher","das_tickbox":"1","isi":1,"author":[{"full_name":"Shimura, Yosuke","first_name":"Yosuke","last_name":"Shimura"},{"last_name":"Godfrin","first_name":"Clement","full_name":"Godfrin, Clement"},{"last_name":"Hikavyy","full_name":"Hikavyy, Andriy","first_name":"Andriy"},{"first_name":"Roy","full_name":"Li, Roy","last_name":"Li"},{"orcid":"0000-0002-2862-8372","id":"2A67C376-F248-11E8-B48F-1D18A9856A87","last_name":"Aguilera Servin","first_name":"Juan L","full_name":"Aguilera Servin, Juan L"},{"full_name":"Katsaros, Georgios","first_name":"Georgios","orcid":"0000-0001-8342-202X","id":"38DB5788-F248-11E8-B48F-1D18A9856A87","last_name":"Katsaros"},{"last_name":"Favia","first_name":"Paola","full_name":"Favia, Paola"},{"last_name":"Han","first_name":"Han","full_name":"Han, Han"},{"last_name":"Wan","first_name":"Danny","full_name":"Wan, Danny"},{"first_name":"Kristiaan","full_name":"de Greve, Kristiaan","last_name":"de Greve"},{"full_name":"Loo, Roger","first_name":"Roger","last_name":"Loo"}],"day":"20","article_type":"original","OA_type":"hybrid","file":[{"checksum":"62e8e9ae960387a3dca32ec7f5e413ab","relation":"main_file","date_updated":"2024-07-22T11:56:08Z","file_name":"2024_MaterialsScience_Shimura.pdf","access_level":"open_access","date_created":"2024-07-22T11:56:08Z","creator":"dernst","file_size":4220165,"success":1,"content_type":"application/pdf","file_id":"17312"}],"quality_controlled":"1","supplementarymaterial":"no","volume":174,"article_processing_charge":"Yes (in subscription journal)","publication_identifier":{"issn":["1369-8001"]},"abstract":[{"text":"The epitaxial growth of a strained Ge layer, which is a promising candidate for the channel material of a hole spin qubit, has been demonstrated on 300 mm Si wafers using commercially available Si0.3Ge0.7 strain relaxed buffer (SRB) layers. The assessment of the layer and the interface qualities for a buried strained Ge layer embedded in Si0.3Ge0.7 layers is reported. The XRD reciprocal space mapping confirmed that the reduction of the growth temperature enables the 2-dimensional growth of the Ge layer fully strained with respect to the Si0.3Ge0.7. Nevertheless, dislocations at the top and/or bottom interface of the Ge layer were observed by means of electron channeling contrast imaging, suggesting the importance of the careful dislocation assessment. The interface abruptness does not depend on the selection of the precursor gases, but it is strongly influenced by the growth temperature which affects the coverage of the surface H-passivation. The mobility of 2.7 × 105 cm2/Vs is promising, while the low percolation density of 3 × 1010 /cm2 measured with a Hall-bar device at 7 K illustrates the high quality of the heterostructure thanks to the high Si0.3Ge0.7 SRB quality.","lang":"eng"}],"doi":"10.1016/j.mssp.2024.108231","file_date_updated":"2024-07-22T11:56:08Z","citation":{"ama":"Shimura Y, Godfrin C, Hikavyy A, et al. Compressively strained epitaxial Ge layers for quantum computing applications. <i>Materials Science in Semiconductor Processing</i>. 2024;174(5). doi:<a href=\"https://doi.org/10.1016/j.mssp.2024.108231\">10.1016/j.mssp.2024.108231</a>","short":"Y. Shimura, C. Godfrin, A. Hikavyy, R. Li, J.L. Aguilera Servin, G. Katsaros, P. Favia, H. Han, D. Wan, K. de Greve, R. Loo, Materials Science in Semiconductor Processing 174 (2024).","chicago":"Shimura, Yosuke, Clement Godfrin, Andriy Hikavyy, Roy Li, Juan L Aguilera Servin, Georgios Katsaros, Paola Favia, et al. “Compressively Strained Epitaxial Ge Layers for Quantum Computing Applications.” <i>Materials Science in Semiconductor Processing</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.mssp.2024.108231\">https://doi.org/10.1016/j.mssp.2024.108231</a>.","ista":"Shimura Y, Godfrin C, Hikavyy A, Li R, Aguilera Servin JL, Katsaros G, Favia P, Han H, Wan D, de Greve K, Loo R. 2024. Compressively strained epitaxial Ge layers for quantum computing applications. Materials Science in Semiconductor Processing. 174(5), 108231.","ieee":"Y. Shimura <i>et al.</i>, “Compressively strained epitaxial Ge layers for quantum computing applications,” <i>Materials Science in Semiconductor Processing</i>, vol. 174, no. 5. Elsevier, 2024.","apa":"Shimura, Y., Godfrin, C., Hikavyy, A., Li, R., Aguilera Servin, J. L., Katsaros, G., … Loo, R. (2024). Compressively strained epitaxial Ge layers for quantum computing applications. <i>Materials Science in Semiconductor Processing</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.mssp.2024.108231\">https://doi.org/10.1016/j.mssp.2024.108231</a>","mla":"Shimura, Yosuke, et al. “Compressively Strained Epitaxial Ge Layers for Quantum Computing Applications.” <i>Materials Science in Semiconductor Processing</i>, vol. 174, no. 5, 108231, Elsevier, 2024, doi:<a href=\"https://doi.org/10.1016/j.mssp.2024.108231\">10.1016/j.mssp.2024.108231</a>."},"keyword":["Mechanical Engineering","Mechanics of Materials","Condensed Matter Physics","General Materials Science"],"department":[{"_id":"GeKa"},{"_id":"NanoFab"}],"has_accepted_license":"1","ddc":["530"],"date_updated":"2026-10-02T11:06:21Z","_id":"15018","publisher":"Elsevier","external_id":{"isi":["001188520000001"]},"acknowledgement":"The Ge project received funding from the European Union's Horizon Europe programme under the Grant Agreement 101069515 – IGNITE. Siltronic AG is acknowledged for providing the SRB wafers. This work was supported by Imec's Industrial Affiliation Program on Quantum Computing.","title":"Compressively strained epitaxial Ge layers for quantum computing applications","oa_version":"Published Version","language":[{"iso":"eng"}],"month":"05","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","scopus_import":"1","project":[{"name":"Integrated Germanium Quantum Technology","_id":"34c0acea-11ca-11ed-8bc3-8775e10fd452","grant_number":"101069515"}],"dataavailabilitystatement":"No data was used for the research described in the article.","article_number":"108231"},{"_id":"14979","publisher":"Springer Nature","date_updated":"2026-10-02T11:21:19Z","ddc":["570"],"acknowledgement":"We thank A. Bergthaler (Research Center for Molecular Medicine of the Austrian Academy of Sciences) for providing VACV WR. We thank A. Nicholas and his team at the ISTA proteomics facility, and S. Elefante at the ISTA Scientific Computing facility for their support. We also thank F. Fäßler, D. Porley, T. Muthspiel and other members of the Schur group for support and helpful discussions. We also thank D. Castaño-Díez for support with Dynamo. We thank D. Farrell for his help optimizing the Rosetta protocol to refine the atomic model into the cryo-EM map with symmetry.\r\n\r\nF.K.M.S. acknowledges support from ISTA and EMBO. F.K.M.S. also received support from the Austrian Science Fund (FWF) grant P31445. This publication has been made possible in part by CZI grant DAF2021-234754 and grant https://doi.org/10.37921/812628ebpcwg from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation (funder https://doi.org/10.13039/100014989) awarded to F.K.M.S.\r\n\r\nThis research was also supported by the Scientific Service Units (SSUs) of ISTA through resources provided by Scientific Computing (SciComp), the Life Science Facility (LSF), and the Electron Microscopy Facility (EMF). We also acknowledge the use of COSMIC45 and Colabfold46.","external_id":{"isi":["001158144600002"],"pmid":["38316877"]},"APC_amount":"11700 EUR","title":"Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores","article_processing_charge":"Yes (in subscription journal)","file_date_updated":"2024-07-22T11:27:22Z","doi":"10.1038/s41594-023-01201-6","citation":{"ieee":"J. Datler <i>et al.</i>, “Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores,” <i>Nature Structural &#38; Molecular Biology</i>, vol. 31. Springer Nature, pp. 1114–1123, 2024.","ista":"Datler J, Hansen J, Thader A, Schlögl A, Bauer LW, Hodirnau V-V, Schur FK. 2024. Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores. Nature Structural &#38; Molecular Biology. 31, 1114–1123.","short":"J. Datler, J. Hansen, A. Thader, A. Schlögl, L.W. Bauer, V.-V. Hodirnau, F.K. Schur, Nature Structural &#38; Molecular Biology 31 (2024) 1114–1123.","chicago":"Datler, Julia, Jesse Hansen, Andreas Thader, Alois Schlögl, Lukas W Bauer, Victor-Valentin Hodirnau, and Florian KM Schur. “Multi-Modal Cryo-EM Reveals Trimers of Protein A10 to Form the Palisade Layer in Poxvirus Cores.” <i>Nature Structural &#38; Molecular Biology</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41594-023-01201-6\">https://doi.org/10.1038/s41594-023-01201-6</a>.","ama":"Datler J, Hansen J, Thader A, et al. Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores. <i>Nature Structural &#38; Molecular Biology</i>. 2024;31:1114-1123. doi:<a href=\"https://doi.org/10.1038/s41594-023-01201-6\">10.1038/s41594-023-01201-6</a>","mla":"Datler, Julia, et al. “Multi-Modal Cryo-EM Reveals Trimers of Protein A10 to Form the Palisade Layer in Poxvirus Cores.” <i>Nature Structural &#38; Molecular Biology</i>, vol. 31, Springer Nature, 2024, pp. 1114–23, doi:<a href=\"https://doi.org/10.1038/s41594-023-01201-6\">10.1038/s41594-023-01201-6</a>.","apa":"Datler, J., Hansen, J., Thader, A., Schlögl, A., Bauer, L. W., Hodirnau, V.-V., &#38; Schur, F. K. (2024). Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores. <i>Nature Structural &#38; Molecular Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41594-023-01201-6\">https://doi.org/10.1038/s41594-023-01201-6</a>"},"publication_identifier":{"issn":["1545-9993"],"eissn":["1545-9985"]},"abstract":[{"lang":"eng","text":"Poxviruses are among the largest double-stranded DNA viruses, with members such as variola virus, monkeypox virus and the vaccination strain vaccinia virus (VACV). Knowledge about the structural proteins that form the viral core has remained sparse. While major core proteins have been annotated via indirect experimental evidence, their structures have remained elusive and they could not be assigned to individual core features. Hence, which proteins constitute which layers of the core, such as the palisade layer and the inner core wall, has remained enigmatic. Here we show, using a multi-modal cryo-electron microscopy (cryo-EM) approach in combination with AlphaFold molecular modeling, that trimers formed by the cleavage product of VACV protein A10 are the key component of the palisade layer. This allows us to place previously obtained descriptions of protein interactions within the core wall into perspective and to provide a detailed model of poxvirus core architecture. Importantly, we show that interactions within A10 trimers are likely generalizable over members of orthopox- and parapoxviruses."}],"corr_author":"1","keyword":["Molecular Biology","Structural Biology"],"has_accepted_license":"1","department":[{"_id":"FlSc"},{"_id":"ScienComp"},{"_id":"EM-Fac"}],"project":[{"grant_number":"P31445","name":"Structural conservation and diversity in retroviral capsid","_id":"26736D6A-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"dataavailabilitystatement":"The electron microscopy density maps of the A10 trimer and the hexameric flower-shaped pore, the subtomogram average of the palisade layer and representative tomograms for complete viruses as well as isolated cores have been deposited in the Electron Microscopy Data Bank under accession codes: EMD-17410, EMD-17411, EMD-17412, EMD-17413, EMD-17414 and EMD-18452.\r\n\r\nThe refined model of the A10 trimer has been deposited in the Protein Data Bank accession code: PDB 8P4K.\r\n\r\nThe UniProt codes of VACV core proteins used for structure prediction are: A10 (P16715), A3 (P06440), A4 (P29191) and L4 (P03295).\r\n\r\nGenBank Protein IDs of variola virus A10 (ABF23487.1), monkeypox virus A10 (YP_010377118.1), rabbitpox virus A10 (AAS49831.1), cowpox virus A10 (ADZ29251.1), ectromelia virus A10 (NP_671631.1), orf virus P4a (AY386264.1), Amsacta moorei entomopoxvirus AMV139 (NP_064921.1) and Melanoplus sanguinipes entomopoxvirus putative core protein P4a homolog (AF063866.1) were used for protein sequence alignment. Source data for MS experiments are provided as Supplementary Information accompanying this manuscript.","oa_version":"Published Version","month":"07","language":[{"iso":"eng"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","scopus_import":"1","related_material":{"link":[{"url":"https://ista.ac.at/en/news/down-to-the-core-of-poxviruses/","relation":"press_release","description":"News on ISTA Website"}],"record":[{"id":"18766","relation":"dissertation_contains","status":"public"}]},"intvolume":"        31","researchdata_availability":"yes","year":"2024","status":"public","type":"journal_article","date_created":"2024-02-12T09:59:45Z","oa":1,"date_published":"2024-07-01T00:00:00Z","publication_status":"published","fulldoi":"https://doi.org/10.1038/s41594-023-01201-6","publication":"Nature Structural & Molecular Biology","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"article_type":"original","OA_type":"hybrid","pmid":1,"quality_controlled":"1","file":[{"checksum":"bda7bf65d81455480efaed8ca293b0db","relation":"main_file","date_updated":"2024-07-22T11:27:22Z","file_name":"2024_NatureStrucBio_Datler.pdf","access_level":"open_access","date_created":"2024-07-22T11:27:22Z","creator":"dernst","file_size":17485494,"success":1,"file_id":"17307","content_type":"application/pdf"}],"volume":31,"supplementarymaterial":"yes","OA_place":"publisher","das_tickbox":"1","page":"1114-1123","author":[{"first_name":"Julia","full_name":"Datler, Julia","last_name":"Datler","id":"3B12E2E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3616-8580"},{"full_name":"Hansen, Jesse","first_name":"Jesse","last_name":"Hansen","orcid":"0000-0001-7967-2085","id":"1063c618-6f9b-11ec-9123-f912fccded63"},{"first_name":"Andreas","full_name":"Thader, Andreas","id":"3A18A7B8-F248-11E8-B48F-1D18A9856A87","last_name":"Thader"},{"full_name":"Schlögl, Alois","first_name":"Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5621-8100","last_name":"Schlögl"},{"full_name":"Bauer, Lukas W","first_name":"Lukas W","id":"0c894dcf-897b-11ed-a09c-8186353224b0","last_name":"Bauer"},{"full_name":"Hodirnau, Victor-Valentin","first_name":"Victor-Valentin","id":"3661B498-F248-11E8-B48F-1D18A9856A87","last_name":"Hodirnau","orcid":"0000-0003-3904-947X"},{"first_name":"Florian KM","full_name":"Schur, Florian KM","last_name":"Schur","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4790-8078"}],"isi":1,"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"day":"01"},{"oa_version":"Published Version","language":[{"iso":"eng"}],"month":"12","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","scopus_import":"1","dataavailabilitystatement":"All data generated and analysed during this study are included in this published article and its supplementary information files. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD052766 (access details are provided in Suppl. Data File 1). The raw datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.","article_number":"434","DOAJ_listed":"1","article_processing_charge":"Yes","abstract":[{"text":"Background: Human induced pluripotent stem cells represent a scalable source of youthful tissue progenitors and secretomes for regenerative therapies. The aim of our study was to investigate the potential of conditioned medium (CM) from hiPSC-mesenchymal progenitors (hiPSC-MPs) to stimulate osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (MSCs). We also investigated whether prolonged cultivation or osteogenic pre-differentiation of hiPSC-MPs could enhance the stimulatory activity of CM.\r\nMethods: MSCs were isolated from 13 donors (age 20–90 years). CM derived from hiPSC-MPs was added to the MSC cultures and the effects on proliferation and osteogenic differentiation were examined after 14 days and 6 weeks. The stimulatory activity of hiPSC-MP-CM was compared with the activity of MSC-derived CM and with the activity of CM prepared from hiPSC-MPs pre-cultured in growth or osteogenic medium for 14 days. Comparative proteomic analysis of CM was performed to gain insight into the molecular components responsible for the stimulatory activity.\r\nResults: Primary bone marrow-derived MSC exhibited variability, with a tendency towards lower proliferation and tri-lineage differentiation in older donors. hiPSC-MP-CM increased the proliferation and alkaline phosphatase activity of MSC from several adult/aged donors after 14 days of continuous supplementation under osteogenic conditions. However, CM supplementation failed to improve the mineralization of MSC pellets after 6 weeks under osteogenic conditions. hiPSC-MP-CM showed greater enhancement of proliferation and ALP activity than CM derived from bone marrow-derived MSCs. Moreover, 14-day cultivation but not osteogenic pre-differentiation of hiPSC-MPs strongly enhanced CM stimulatory activity. Quantitative proteomic analysis of d14-CM revealed a distinct profile of components that formed a highly interconnected associations network with two clusters, one functionally associated with binding and organization of actin/cytoskeletal components and the other with structural constituents of the extracellular matrix, collagen, and growth factor binding. Several hub proteins were identified that were reported to have functions in cell-extracellular matrix interaction, osteogenic differentiation and development.\r\nConclusions: Our data show that hiPSC-MP-CM enhances early osteogenic differentiation of human bone marrow-derived MSCs and that prolonged cultivation of hiPSC-MPs enhances CM-stimulatory activity. Proteomic analysis of the upregulated protein components provides the basis for further optimization of hiPSC-MP-CM for bone regenerative therapies.","lang":"eng"}],"publication_identifier":{"eissn":["1757-6512"]},"file_date_updated":"2024-12-10T08:28:17Z","doi":"10.1186/s13287-024-03960-5","citation":{"apa":"Marolt Presen, D., Goeschl, V., Hanetseder, D., Ogrin, L., Stetco, A. L., Tansek, A., … Redl, H. (2024). Prolonged cultivation enhances the stimulatory activity of hiPSC mesenchymal progenitor-derived conditioned medium. <i>Stem Cell Research and Therapy</i>. Springer Nature. <a href=\"https://doi.org/10.1186/s13287-024-03960-5\">https://doi.org/10.1186/s13287-024-03960-5</a>","mla":"Marolt Presen, Darja, et al. “Prolonged Cultivation Enhances the Stimulatory Activity of HiPSC Mesenchymal Progenitor-Derived Conditioned Medium.” <i>Stem Cell Research and Therapy</i>, vol. 15, 434, Springer Nature, 2024, doi:<a href=\"https://doi.org/10.1186/s13287-024-03960-5\">10.1186/s13287-024-03960-5</a>.","ama":"Marolt Presen D, Goeschl V, Hanetseder D, et al. Prolonged cultivation enhances the stimulatory activity of hiPSC mesenchymal progenitor-derived conditioned medium. <i>Stem Cell Research and Therapy</i>. 2024;15. doi:<a href=\"https://doi.org/10.1186/s13287-024-03960-5\">10.1186/s13287-024-03960-5</a>","chicago":"Marolt Presen, Darja, Vanessa Goeschl, Dominik Hanetseder, Laura Ogrin, Alexandra Larissa Stetco, Anja Tansek, Laura Pozenel, et al. “Prolonged Cultivation Enhances the Stimulatory Activity of HiPSC Mesenchymal Progenitor-Derived Conditioned Medium.” <i>Stem Cell Research and Therapy</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1186/s13287-024-03960-5\">https://doi.org/10.1186/s13287-024-03960-5</a>.","short":"D. Marolt Presen, V. Goeschl, D. Hanetseder, L. Ogrin, A.L. Stetco, A. Tansek, L. Pozenel, B. Bruszel, G. Mitulovic, J. Oesterreicher, J. Zipperle, B. Schaedl, W. Holnthoner, J. Grillari, H. Redl, Stem Cell Research and Therapy 15 (2024).","ista":"Marolt Presen D, Goeschl V, Hanetseder D, Ogrin L, Stetco AL, Tansek A, Pozenel L, Bruszel B, Mitulovic G, Oesterreicher J, Zipperle J, Schaedl B, Holnthoner W, Grillari J, Redl H. 2024. Prolonged cultivation enhances the stimulatory activity of hiPSC mesenchymal progenitor-derived conditioned medium. Stem Cell Research and Therapy. 15, 434.","ieee":"D. Marolt Presen <i>et al.</i>, “Prolonged cultivation enhances the stimulatory activity of hiPSC mesenchymal progenitor-derived conditioned medium,” <i>Stem Cell Research and Therapy</i>, vol. 15. Springer Nature, 2024."},"department":[{"_id":"LifeSc"}],"has_accepted_license":"1","date_updated":"2026-10-16T08:56:29Z","ddc":["570"],"_id":"18581","publisher":"Springer Nature","external_id":{"pmid":["39551765"],"isi":["001356479400001"]},"acknowledgement":"We thank the personnel of the Lorenz-Böhler-Unfallkrankenhaus for providing the human tissue waste for primary cell isolation and the New York Stem Cell Foundation Research Institute for providing the human induced pluripotent stem cell line 1013 A and its mesenchymal progenitors. We also thank all our colleagues at the Ludwig Boltzmann Institute for Traumatology for their suggestions and ongoing support of the project. InstaText writing tool (https://instatext.io) was used to edit the English language of the final manuscript.\r\nThis work has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie actions (grant agreement No. 657716) and the Transforming European Industry call H2020-NMBP-TRIND-2020 (grant agreement No. 953134), as well as by the FFG Industrienahe Dissertation program (grant agreement No. 867803 and 853056), the FEMtech Praktika program (grant agreement No. 852154, 868917 and 877951) and the Production of the Future program (grant agreement No. 877452).","title":"Prolonged cultivation enhances the stimulatory activity of hiPSC mesenchymal progenitor-derived conditioned medium","OA_place":"publisher","das_tickbox":"1","isi":1,"author":[{"last_name":"Marolt Presen","first_name":"Darja","full_name":"Marolt Presen, Darja"},{"full_name":"Goeschl, Vanessa","first_name":"Vanessa","last_name":"Goeschl"},{"last_name":"Hanetseder","first_name":"Dominik","full_name":"Hanetseder, Dominik"},{"last_name":"Ogrin","first_name":"Laura","full_name":"Ogrin, Laura"},{"full_name":"Stetco, Alexandra Larissa","first_name":"Alexandra Larissa","last_name":"Stetco"},{"first_name":"Anja","full_name":"Tansek, Anja","last_name":"Tansek"},{"last_name":"Pozenel","full_name":"Pozenel, Laura","first_name":"Laura"},{"full_name":"Bruszel, Bella","first_name":"Bella","id":"70abbbb3-88ea-11ec-8e0a-e8c939944834","last_name":"Bruszel"},{"first_name":"Goran","full_name":"Mitulovic, Goran","last_name":"Mitulovic"},{"last_name":"Oesterreicher","first_name":"Johannes","full_name":"Oesterreicher, Johannes"},{"last_name":"Zipperle","full_name":"Zipperle, Johannes","first_name":"Johannes"},{"full_name":"Schaedl, Barbara","first_name":"Barbara","last_name":"Schaedl"},{"first_name":"Wolfgang","full_name":"Holnthoner, Wolfgang","last_name":"Holnthoner"},{"last_name":"Grillari","first_name":"Johannes","full_name":"Grillari, Johannes"},{"first_name":"Heinz","full_name":"Redl, Heinz","last_name":"Redl"}],"day":"01","pmid":1,"article_type":"original","OA_type":"gold","file":[{"content_type":"application/pdf","file_id":"18641","success":1,"file_size":6690494,"creator":"dernst","access_level":"open_access","date_created":"2024-12-10T08:28:17Z","file_name":"2024_StemCellResearch_Presen.pdf","checksum":"91edba8edde30d781dce89fdd5cadc39","relation":"main_file","date_updated":"2024-12-10T08:28:17Z"}],"quality_controlled":"1","supplementarymaterial":"yes","volume":15,"fulldoi":"https://doi.org/10.1186/s13287-024-03960-5","publication_status":"published","tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"publication":"Stem Cell Research and Therapy","status":"public","year":"2024","researchdata_availability":"yes","intvolume":"        15","type":"journal_article","date_created":"2024-11-24T23:01:47Z","date_published":"2024-12-01T00:00:00Z","oa":1}]