[{"file":[{"content_type":"application/pdf","file_name":"2024_eLife_Kulich.pdf","date_updated":"2024-04-03T13:18:00Z","creator":"dernst","file_id":"15288","checksum":"a73a84d3bf97a6d09d24308ca6dd0a0c","date_created":"2024-04-03T13:18:00Z","file_size":11451904,"relation":"main_file","access_level":"open_access","success":1}],"ddc":["580"],"pmid":1,"intvolume":"        12","status":"public","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"date_created":"2024-04-02T11:35:58Z","scopus_import":"1","has_accepted_license":"1","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"publication":"eLife","language":[{"iso":"eng"}],"file_date_updated":"2024-04-03T13:18:00Z","corr_author":"1","acknowledgement":"The research leading to these results has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme grant agreement No 742985 and Austrian Science Fund (FWF): I3630-775 B25 to J.F. This research was also supported by the Lab Support Facility (LSF) and the Imaging and Optics Facility (IOF) of IST Austria, namely Tereza Bělinová for her help with the imaging. JS was supported by FemTECH fellowship.","author":[{"first_name":"Ivan","last_name":"Kulich","id":"57a1567c-8314-11eb-9063-c9ddc3451a54","full_name":"Kulich, Ivan"},{"id":"07cf4637-baaf-11ee-9227-e1de57d1d69b","full_name":"Schmid, Julia","last_name":"Schmid","first_name":"Julia"},{"first_name":"Anastasiia","full_name":"Teplova, Anastasiia","id":"e3736151-106c-11ec-b916-c2558e2762c6","last_name":"Teplova"},{"full_name":"Qi, Linlin","id":"44B04502-A9ED-11E9-B6FC-583AE6697425","last_name":"Qi","first_name":"Linlin","orcid":"0000-0001-5187-8401"},{"first_name":"Jiří","orcid":"0000-0002-8302-7596","full_name":"Friml, Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","last_name":"Friml"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"journal_article","related_material":{"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/beneath-the-surface/","description":"News on ISTA website"}]},"oa":1,"_id":"15257","DOAJ_listed":"1","abstract":[{"lang":"eng","text":"Root gravitropic bending represents a fundamental aspect of terrestrial plant physiology. Gravity is perceived by sedimentation of starch-rich plastids (statoliths) to the bottom of the central root cap cells. Following gravity perception, intercellular auxin transport is redirected downwards leading to an asymmetric auxin accumulation at the lower root side causing inhibition of cell expansion, ultimately resulting in downwards bending. How gravity-induced statoliths repositioning is translated into asymmetric auxin distribution remains unclear despite PIN auxin efflux carriers and the Negative Gravitropic Response of roots (NGR) proteins polarize along statolith sedimentation, thus providing a plausible mechanism for auxin flow redirection. In this study, using a functional NGR1-GFP construct, we visualized the NGR1 localization on the statolith surface and plasma membrane (PM) domains in close proximity to the statoliths, correlating with their movements. We determined that NGR1 binding to these PM domains is indispensable for NGR1 functionality and relies on cysteine acylation and adjacent polybasic regions as well as on lipid and sterol PM composition. Detailed timing of the early events following graviperception suggested that both NGR1 repolarization and initial auxin asymmetry precede the visible PIN3 polarization. This discrepancy motivated us to unveil a rapid, NGR-dependent translocation of PIN-activating AGCVIII kinase D6PK towards lower PMs of gravity-perceiving cells, thus providing an attractive model for rapid redirection of auxin fluxes following gravistimulation."}],"article_type":"original","oa_version":"Published Version","day":"05","volume":12,"ec_funded":1,"quality_controlled":"1","external_id":{"pmid":["38441122"]},"project":[{"name":"Tracing Evolution of Auxin Transport and Polarity in Plants","call_identifier":"H2020","_id":"261099A6-B435-11E9-9278-68D0E5697425","grant_number":"742985"},{"_id":"26538374-B435-11E9-9278-68D0E5697425","name":"Molecular mechanisms of endocytic cargo recognition in plants","call_identifier":"FWF","grant_number":"I03630"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"date_updated":"2025-04-23T07:45:02Z","month":"03","department":[{"_id":"JiFr"}],"title":"Rapid translocation of NGR proteins driving polarization of PIN-activating D6 protein kinase during root gravitropism","article_number":"91523","year":"2024","date_published":"2024-03-05T00:00:00Z","citation":{"ista":"Kulich I, Schmid J, Teplova A, Qi L, Friml J. 2024. Rapid translocation of NGR proteins driving polarization of PIN-activating D6 protein kinase during root gravitropism. eLife. 12, 91523.","mla":"Kulich, Ivan, et al. “Rapid Translocation of NGR Proteins Driving Polarization of PIN-Activating D6 Protein Kinase during Root Gravitropism.” <i>ELife</i>, vol. 12, 91523, eLife Sciences Publications, 2024, doi:<a href=\"https://doi.org/10.7554/elife.91523\">10.7554/elife.91523</a>.","ieee":"I. Kulich, J. Schmid, A. Teplova, L. Qi, and J. Friml, “Rapid translocation of NGR proteins driving polarization of PIN-activating D6 protein kinase during root gravitropism,” <i>eLife</i>, vol. 12. eLife Sciences Publications, 2024.","apa":"Kulich, I., Schmid, J., Teplova, A., Qi, L., &#38; Friml, J. (2024). Rapid translocation of NGR proteins driving polarization of PIN-activating D6 protein kinase during root gravitropism. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.91523\">https://doi.org/10.7554/elife.91523</a>","short":"I. Kulich, J. Schmid, A. Teplova, L. Qi, J. Friml, ELife 12 (2024).","chicago":"Kulich, Ivan, Julia Schmid, Anastasiia Teplova, Linlin Qi, and Jiří Friml. “Rapid Translocation of NGR Proteins Driving Polarization of PIN-Activating D6 Protein Kinase during Root Gravitropism.” <i>ELife</i>. eLife Sciences Publications, 2024. <a href=\"https://doi.org/10.7554/elife.91523\">https://doi.org/10.7554/elife.91523</a>.","ama":"Kulich I, Schmid J, Teplova A, Qi L, Friml J. Rapid translocation of NGR proteins driving polarization of PIN-activating D6 protein kinase during root gravitropism. <i>eLife</i>. 2024;12. doi:<a href=\"https://doi.org/10.7554/elife.91523\">10.7554/elife.91523</a>"},"publication_status":"published","publication_identifier":{"issn":["2050-084X"]},"publisher":"eLife Sciences Publications","article_processing_charge":"Yes","doi":"10.7554/elife.91523"},{"author":[{"last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole","first_name":"Nicole","orcid":"0000-0002-3183-8207"},{"last_name":"Cheung","id":"471195F6-F248-11E8-B48F-1D18A9856A87","full_name":"Cheung, Giselle T","first_name":"Giselle T","orcid":"0000-0001-8457-2572"},{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","first_name":"Simon"}],"acknowledgement":"This research was supported by the Scientific Service Units (SSU) at IST Austria through resources provided by the Imaging & Optics Facility (IOF) and Preclinical Facilities (PCF). N.A. received support from FWF Firnberg-Programme (T 1031). G.C. received support from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411 as an ISTplus postdoctoral fellow. This work was also supported by IST Austria institutional funds, FWF SFB F78 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 725780 LinPro) to S.H.","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"journal_article","file_date_updated":"2024-07-16T11:50:03Z","corr_author":"1","issue":"1","_id":"14683","oa":1,"intvolume":"         5","pmid":1,"file":[{"date_created":"2024-07-16T11:50:03Z","checksum":"3f0ee62e04bf5a44b45b035662826e95","access_level":"open_access","success":1,"relation":"main_file","file_size":8871807,"date_updated":"2024-07-16T11:50:03Z","file_name":"2024_STARProtoc_Amberg.pdf","content_type":"application/pdf","creator":"dernst","file_id":"17260"}],"ddc":["570"],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"has_accepted_license":"1","publication":"STAR Protocols","language":[{"iso":"eng"}],"date_created":"2023-12-13T11:48:05Z","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Neuroscience"],"scopus_import":"1","status":"public","title":"Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry","article_number":"102771","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"date_updated":"2025-04-15T08:23:06Z","department":[{"_id":"SiHi"}],"month":"03","publication_status":"published","article_processing_charge":"Yes (in subscription journal)","publisher":"Elsevier","publication_identifier":{"issn":["2666-1667"]},"doi":"10.1016/j.xpro.2023.102771","date_published":"2024-03-15T00:00:00Z","year":"2024","citation":{"ista":"Amberg N, Cheung GT, Hippenmeyer S. 2024. Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. STAR Protocols. 5(1), 102771.","mla":"Amberg, Nicole, et al. “Protocol for Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers by Flow Cytometry.” <i>STAR Protocols</i>, vol. 5, no. 1, 102771, Elsevier, 2024, doi:<a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">10.1016/j.xpro.2023.102771</a>.","ieee":"N. Amberg, G. T. Cheung, and S. Hippenmeyer, “Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry,” <i>STAR Protocols</i>, vol. 5, no. 1. Elsevier, 2024.","apa":"Amberg, N., Cheung, G. T., &#38; Hippenmeyer, S. (2024). Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">https://doi.org/10.1016/j.xpro.2023.102771</a>","short":"N. Amberg, G.T. Cheung, S. Hippenmeyer, STAR Protocols 5 (2024).","chicago":"Amberg, Nicole, Giselle T Cheung, and Simon Hippenmeyer. “Protocol for Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers by Flow Cytometry.” <i>STAR Protocols</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">https://doi.org/10.1016/j.xpro.2023.102771</a>.","ama":"Amberg N, Cheung GT, Hippenmeyer S. Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. <i>STAR Protocols</i>. 2024;5(1). doi:<a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">10.1016/j.xpro.2023.102771</a>"},"abstract":[{"lang":"eng","text":"Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice and high-resolution phenotyping at the individual cell level. Here, we present a protocol for isolating MADM-labeled cells with high yield for downstream molecular analyses using fluorescence-activated cell sorting (FACS). We describe steps for generating MADM-labeled mice, perfusion, single-cell suspension, and debris removal. We then detail procedures for cell sorting by FACS and downstream analysis. This protocol is suitable for embryonic to adult mice.\r\nFor complete details on the use and execution of this protocol, please refer to Contreras et al. (2021).1"}],"article_type":"review","external_id":{"pmid":["38070137"]},"quality_controlled":"1","project":[{"grant_number":"T01031","name":"Role of Eed in neural stem cell lineage progression","call_identifier":"FWF","_id":"268F8446-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"},{"grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression"},{"grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425"}],"volume":5,"oa_version":"Published Version","day":"15","ec_funded":1},{"abstract":[{"text":"The GNOM (GN) Guanine nucleotide Exchange Factor for ARF small GTPases (ARF-GEF) is among the best studied trafficking regulators in plants, playing crucial and unique developmental roles in patterning and polarity. The current models place GN at the Golgi apparatus (GA), where it mediates secretion/recycling, and at the plasma membrane (PM) presumably contributing to clathrin-mediated endocytosis (CME). The mechanistic basis of the developmental function of GN, distinct from the other ARF-GEFs including its closest homologue GNOM-LIKE1 (GNL1), remains elusive. Insights from this study largely extend the current notions of GN function. We show that GN, but not GNL1, localizes to the cell periphery at long-lived structures distinct from clathrin-coated pits, while CME and secretion proceed normally in <jats:italic>gn</jats:italic> knockouts. The functional GN mutant variant GN<jats:sup>fewerroots</jats:sup>, absent from the GA, suggests that the cell periphery is the major site of GN action responsible for its developmental function. Following inhibition by Brefeldin A, GN, but not GNL1, relocates to the PM likely on exocytic vesicles, suggesting selective molecular associations en route to the cell periphery. A study of GN-GNL1 chimeric ARF-GEFs indicates that all GN domains contribute to the specific GN function in a partially redundant manner. Together, this study offers significant steps toward the elucidation of the mechanism underlying unique cellular and development functions of GNOM.","lang":"eng"}],"article_type":"original","OA_type":"gold","oa_version":"Published Version","volume":13,"day":"21","ec_funded":1,"quality_controlled":"1","external_id":{"isi":["001174278000001"],"pmid":["38381485"]},"project":[{"grant_number":"742985","name":"Tracing Evolution of Auxin Transport and Polarity in Plants","_id":"261099A6-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"I03630","name":"Molecular mechanisms of endocytic cargo recognition in plants","call_identifier":"FWF","_id":"26538374-B435-11E9-9278-68D0E5697425"},{"_id":"3AC91DDA-15DF-11EA-824D-93A3E7B544D1","name":"FWF Open Access Fund","call_identifier":"FWF"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"date_updated":"2025-10-15T06:31:47Z","month":"02","department":[{"_id":"JiFr"}],"title":"Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery","isi":1,"date_published":"2024-02-21T00:00:00Z","year":"2024","citation":{"mla":"Adamowski, Maciek, et al. “Developmental Patterning Function of GNOM ARF-GEF Mediated from the Cell Periphery.” <i>ELife</i>, vol. 13, eLife Sciences Publications, 2024, doi:<a href=\"https://doi.org/10.7554/elife.68993\">10.7554/elife.68993</a>.","ieee":"M. Adamowski, I. Matijevic, and J. Friml, “Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery,” <i>eLife</i>, vol. 13. eLife Sciences Publications, 2024.","ista":"Adamowski M, Matijevic I, Friml J. 2024. Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. eLife. 13.","chicago":"Adamowski, Maciek, Ivana Matijevic, and Jiří Friml. “Developmental Patterning Function of GNOM ARF-GEF Mediated from the Cell Periphery.” <i>ELife</i>. eLife Sciences Publications, 2024. <a href=\"https://doi.org/10.7554/elife.68993\">https://doi.org/10.7554/elife.68993</a>.","ama":"Adamowski M, Matijevic I, Friml J. Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. <i>eLife</i>. 2024;13. doi:<a href=\"https://doi.org/10.7554/elife.68993\">10.7554/elife.68993</a>","apa":"Adamowski, M., Matijevic, I., &#38; Friml, J. (2024). Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.68993\">https://doi.org/10.7554/elife.68993</a>","short":"M. Adamowski, I. Matijevic, J. Friml, ELife 13 (2024)."},"publication_status":"published","article_processing_charge":"Yes","publisher":"eLife Sciences Publications","publication_identifier":{"issn":["2050-084X"]},"doi":"10.7554/elife.68993","file":[{"file_id":"17310","creator":"dernst","file_name":"2024_eLife_Adamowski.pdf","date_updated":"2024-07-22T11:51:50Z","content_type":"application/pdf","success":1,"access_level":"open_access","relation":"main_file","file_size":15675744,"date_created":"2024-07-22T11:51:50Z","checksum":"b2b2d583b433823af731842f1420113e"}],"ddc":["580"],"intvolume":"        13","pmid":1,"date_created":"2024-02-27T07:10:11Z","scopus_import":"1","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"status":"public","APC_amount":"2792,52 EUR","has_accepted_license":"1","publication":"eLife","language":[{"iso":"eng"}],"file_date_updated":"2024-07-22T11:51:50Z","corr_author":"1","author":[{"full_name":"Adamowski, Maciek","id":"45F536D2-F248-11E8-B48F-1D18A9856A87","last_name":"Adamowski","orcid":"0000-0001-6463-5257","first_name":"Maciek"},{"last_name":"Matijevic","id":"83c17ce3-15b2-11ec-abd3-f486545870bd","full_name":"Matijevic, Ivana","first_name":"Ivana"},{"last_name":"Friml","full_name":"Friml, Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","first_name":"Jiří","orcid":"0000-0002-8302-7596"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","acknowledgement":"The authors would like to gratefully acknowledge Dr Xixi Zhang for cloning the GNL1/pDONR221 construct and for useful discussions.H2020 European Research Council Advanced Grant ETAP742985 to Jiří Friml, Austrian Science Fund I 3630-B25 to Jiří Friml","type":"journal_article","oa":1,"_id":"15033","OA_place":"publisher","DOAJ_listed":"1"},{"keyword":["Physiology","General Neuroscience"],"date_created":"2023-02-15T14:46:14Z","scopus_import":"1","status":"public","publication":"Journal of Neurophysiology","language":[{"iso":"eng"}],"intvolume":"       129","page":"501-512","pmid":1,"_id":"12562","issue":"3","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","author":[{"first_name":"David R.","last_name":"Ladle","full_name":"Ladle, David R."},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","orcid":"0000-0003-2279-1061"}],"acknowledgement":"The authors gratefully thank Dr. Silvia Arber, University of Basel and Friedrich Miescher Institute for Biomedical Research, for support and in whose lab the data were collected. For advice on statistical analysis, we thank Michael Bottomley from the Statistical Consulting Center, College of Science and Mathematics, Wright State University.","type":"journal_article","volume":129,"day":"01","oa_version":"None","external_id":{"pmid":["36695533"],"isi":["000957721600001"]},"quality_controlled":"1","article_type":"original","abstract":[{"lang":"eng","text":"Presynaptic inputs determine the pattern of activation of postsynaptic neurons in a neural circuit. Molecular and genetic pathways that regulate the selective formation of subsets of presynaptic inputs are largely unknown, despite significant understanding of the general process of synaptogenesis. In this study, we have begun to identify such factors using the spinal monosynaptic stretch reflex circuit as a model system. In this neuronal circuit, Ia proprioceptive afferents establish monosynaptic connections with spinal motor neurons that project to the same muscle (termed homonymous connections) or muscles with related or synergistic function. However, monosynaptic connections are not formed with motor neurons innervating muscles with antagonistic functions. The ETS transcription factor ER81 (also known as ETV1) is expressed by all proprioceptive afferents, but only a small set of motor neuron pools in the lumbar spinal cord of the mouse. Here we use conditional mouse genetic techniques to eliminate Er81 expression selectively from motor neurons. We find that ablation of Er81 in motor neurons reduces synaptic inputs from proprioceptive afferents conveying information from homonymous and synergistic muscles, with no change observed in the connectivity pattern from antagonistic proprioceptive afferents. In summary, these findings suggest a role for ER81 in defined motor neuron pools to control the assembly of specific presynaptic inputs and thereby influence the profile of activation of these motor neurons."}],"year":"2023","date_published":"2023-03-01T00:00:00Z","citation":{"ieee":"D. R. Ladle and S. Hippenmeyer, “Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons,” <i>Journal of Neurophysiology</i>, vol. 129, no. 3. American Physiological Society, pp. 501–512, 2023.","mla":"Ladle, David R., and Simon Hippenmeyer. “Loss of ETV1/ER81 in Motor Neurons Leads to Reduced Monosynaptic Inputs from Proprioceptive Sensory Neurons.” <i>Journal of Neurophysiology</i>, vol. 129, no. 3, American Physiological Society, 2023, pp. 501–12, doi:<a href=\"https://doi.org/10.1152/jn.00172.2022\">10.1152/jn.00172.2022</a>.","ista":"Ladle DR, Hippenmeyer S. 2023. Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons. Journal of Neurophysiology. 129(3), 501–512.","ama":"Ladle DR, Hippenmeyer S. Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons. <i>Journal of Neurophysiology</i>. 2023;129(3):501-512. doi:<a href=\"https://doi.org/10.1152/jn.00172.2022\">10.1152/jn.00172.2022</a>","chicago":"Ladle, David R., and Simon Hippenmeyer. “Loss of ETV1/ER81 in Motor Neurons Leads to Reduced Monosynaptic Inputs from Proprioceptive Sensory Neurons.” <i>Journal of Neurophysiology</i>. American Physiological Society, 2023. <a href=\"https://doi.org/10.1152/jn.00172.2022\">https://doi.org/10.1152/jn.00172.2022</a>.","short":"D.R. Ladle, S. Hippenmeyer, Journal of Neurophysiology 129 (2023) 501–512.","apa":"Ladle, D. R., &#38; Hippenmeyer, S. (2023). Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons. <i>Journal of Neurophysiology</i>. American Physiological Society. <a href=\"https://doi.org/10.1152/jn.00172.2022\">https://doi.org/10.1152/jn.00172.2022</a>"},"article_processing_charge":"No","publisher":"American Physiological Society","publication_identifier":{"eissn":["1522-1598"],"issn":["0022-3077"]},"doi":"10.1152/jn.00172.2022","publication_status":"published","date_updated":"2024-10-21T06:01:28Z","month":"03","department":[{"_id":"SiHi"}],"isi":1,"title":"Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons"},{"corr_author":"1","issue":"4","file_date_updated":"2023-08-16T12:29:06Z","author":[{"orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledgement":"I wish to thank all current and past members of the Hippenmeyer laboratory at ISTA for exciting discussions on the subject of this review. I apologize to colleagues whose work I could not cite and/or discuss in the frame of the available space. Work in the Hippenmeyer laboratory on the\r\ndiscussed topic is supported by ISTA institutional funds, FWF SFB F78 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agree-ment no. 725780 LinPro) to SH.","type":"journal_article","oa":1,"_id":"12679","ddc":["570"],"file":[{"content_type":"application/pdf","date_updated":"2023-08-16T12:29:06Z","file_name":"2023_CurrentOpinionNeurobio_Hippenmeyer.pdf","file_id":"14071","creator":"dernst","checksum":"4d11c4ca87e6cbc4d2ac46d3225ea615","date_created":"2023-08-16T12:29:06Z","relation":"main_file","file_size":1787894,"access_level":"open_access","success":1}],"pmid":1,"intvolume":"        79","scopus_import":"1","date_created":"2023-02-26T12:24:21Z","status":"public","keyword":["General Neuroscience"],"publication":"Current Opinion in Neurobiology","language":[{"iso":"eng"}],"has_accepted_license":"1","date_updated":"2025-04-15T08:23:06Z","month":"04","department":[{"_id":"SiHi"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"isi":1,"article_number":"102695","title":"Principles of neural stem cell lineage progression: Insights from developing cerebral cortex","year":"2023","date_published":"2023-04-01T00:00:00Z","citation":{"apa":"Hippenmeyer, S. (2023). Principles of neural stem cell lineage progression: Insights from developing cerebral cortex. <i>Current Opinion in Neurobiology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.conb.2023.102695\">https://doi.org/10.1016/j.conb.2023.102695</a>","short":"S. Hippenmeyer, Current Opinion in Neurobiology 79 (2023).","chicago":"Hippenmeyer, Simon. “Principles of Neural Stem Cell Lineage Progression: Insights from Developing Cerebral Cortex.” <i>Current Opinion in Neurobiology</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.conb.2023.102695\">https://doi.org/10.1016/j.conb.2023.102695</a>.","ama":"Hippenmeyer S. Principles of neural stem cell lineage progression: Insights from developing cerebral cortex. <i>Current Opinion in Neurobiology</i>. 2023;79(4). doi:<a href=\"https://doi.org/10.1016/j.conb.2023.102695\">10.1016/j.conb.2023.102695</a>","ista":"Hippenmeyer S. 2023. Principles of neural stem cell lineage progression: Insights from developing cerebral cortex. Current Opinion in Neurobiology. 79(4), 102695.","mla":"Hippenmeyer, Simon. “Principles of Neural Stem Cell Lineage Progression: Insights from Developing Cerebral Cortex.” <i>Current Opinion in Neurobiology</i>, vol. 79, no. 4, 102695, Elsevier, 2023, doi:<a href=\"https://doi.org/10.1016/j.conb.2023.102695\">10.1016/j.conb.2023.102695</a>.","ieee":"S. Hippenmeyer, “Principles of neural stem cell lineage progression: Insights from developing cerebral cortex,” <i>Current Opinion in Neurobiology</i>, vol. 79, no. 4. Elsevier, 2023."},"article_processing_charge":"Yes (via OA deal)","publisher":"Elsevier","publication_identifier":{"issn":["0959-4388"]},"doi":"10.1016/j.conb.2023.102695","publication_status":"published","article_type":"review","abstract":[{"text":"How to generate a brain of correct size and with appropriate cell-type diversity during development is a major question in Neuroscience. In the developing neocortex, radial glial progenitor (RGP) cells are the main neural stem cells that produce cortical excitatory projection neurons, glial cells, and establish the prospective postnatal stem cell niche in the lateral ventricles. RGPs follow a tightly orchestrated developmental program that when disrupted can result in severe cortical malformations such as microcephaly and megalencephaly. The precise cellular and molecular mechanisms instructing faithful RGP lineage progression are however not well understood. This review will summarize recent conceptual advances that contribute to our understanding of the general principles of RGP lineage progression.","lang":"eng"}],"ec_funded":1,"volume":79,"day":"01","oa_version":"Published Version","external_id":{"pmid":["36842274"],"isi":["000953497700001"]},"quality_controlled":"1","project":[{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F7805"},{"grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}]},{"type":"journal_article","author":[{"first_name":"Verena","last_name":"Hübschmann","id":"32B7C918-F248-11E8-B48F-1D18A9856A87","full_name":"Hübschmann, Verena"},{"orcid":"0000-0003-4309-2251","first_name":"Medina","last_name":"Korkut","full_name":"Korkut, Medina","id":"4B51CE74-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Sandra","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra","last_name":"Siegert"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledgement":"This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung Niederösterreich (grant No. Sc19-017 to V.H.). We thank Rouven Schulz and Alessandro Venturino for their insights into functional assays and data analysis, Verena Seiboth for insights into necessary institutional permission, and ISTA imaging & optics facility (IOF) especially Bernhard Hochreiter for their support.","issue":"4","corr_author":"1","file_date_updated":"2023-01-23T09:50:51Z","_id":"12117","oa":1,"related_material":{"record":[{"status":"public","id":"11478","relation":"other"}]},"intvolume":"         3","pmid":1,"ddc":["570"],"file":[{"file_id":"12340","creator":"dernst","date_updated":"2023-01-23T09:50:51Z","file_name":"2022_STARProtocols_Huebschmann.pdf","content_type":"application/pdf","access_level":"open_access","success":1,"file_size":6251945,"relation":"main_file","date_created":"2023-01-23T09:50:51Z","checksum":"3c71b8a60633d42c2f77c49025d5559b"}],"language":[{"iso":"eng"}],"publication":"STAR Protocols","has_accepted_license":"1","acknowledged_ssus":[{"_id":"Bio"}],"scopus_import":"1","date_created":"2023-01-12T11:56:38Z","status":"public","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Neuroscience"],"article_number":"101866","title":"Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay","month":"12","department":[{"_id":"SaSi"},{"_id":"GradSch"}],"date_updated":"2025-06-11T13:58:47Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"doi":"10.1016/j.xpro.2022.101866","publisher":"Elsevier","publication_identifier":{"issn":["2666-1667"]},"article_processing_charge":"No","publication_status":"published","citation":{"ista":"Hübschmann V, Korkut M, Siegert S. 2022. Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. STAR Protocols. 3(4), 101866.","mla":"Hübschmann, Verena, et al. “Assessing Human IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation Assay.” <i>STAR Protocols</i>, vol. 3, no. 4, 101866, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.xpro.2022.101866\">10.1016/j.xpro.2022.101866</a>.","ieee":"V. Hübschmann, M. Korkut, and S. Siegert, “Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay,” <i>STAR Protocols</i>, vol. 3, no. 4. Elsevier, 2022.","apa":"Hübschmann, V., Korkut, M., &#38; Siegert, S. (2022). Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2022.101866\">https://doi.org/10.1016/j.xpro.2022.101866</a>","short":"V. Hübschmann, M. Korkut, S. Siegert, STAR Protocols 3 (2022).","chicago":"Hübschmann, Verena, Medina Korkut, and Sandra Siegert. “Assessing Human IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation Assay.” <i>STAR Protocols</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.xpro.2022.101866\">https://doi.org/10.1016/j.xpro.2022.101866</a>.","ama":"Hübschmann V, Korkut M, Siegert S. Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. <i>STAR Protocols</i>. 2022;3(4). doi:<a href=\"https://doi.org/10.1016/j.xpro.2022.101866\">10.1016/j.xpro.2022.101866</a>"},"year":"2022","date_published":"2022-12-16T00:00:00Z","article_type":"letter_note","abstract":[{"text":"To understand how potential gene manipulations affect in vitro microglia, we provide a set of short protocols to evaluate microglia identity and function. We detail steps for immunostaining to determine microglia identity. We describe three functional assays for microglia: phagocytosis, calcium response following ATP stimulation, and cytokine expression upon inflammatory stimuli. We apply these protocols to human induced-pluripotent-stem-cell (hiPSC)-derived microglia, but they can be also applied to other in vitro microglial models including primary mouse microglia.\r\nFor complete details on the use and execution of this protocol, please refer to Bartalska et al. (2022).1","lang":"eng"}],"project":[{"name":"Microglia action towards neuronal circuit formation and function in health and disease","_id":"25D4A630-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"715571"},{"grant_number":"SC19-017","name":"How human microglia shape developing neurons during health and inflammation","_id":"9B99D380-BA93-11EA-9121-9846C619BF3A"}],"external_id":{"pmid":["36595902"]},"quality_controlled":"1","ec_funded":1,"oa_version":"Published Version","volume":3,"day":"16"},{"author":[{"id":"fc885ee5-24bf-11eb-ad7b-bcc5104c0c1b","full_name":"Hayward, Laura","last_name":"Hayward","first_name":"Laura"},{"first_name":"Guy","full_name":"Sella, Guy","last_name":"Sella"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","acknowledgement":"We thank Guy Amster, Jeremy Berg, Nick Barton, Yuval Simons and Molly Przeworski for many helpful discussions, and Jeremy Berg, Graham Coop, Joachim Hermisson, Guillaume Martin, Will Milligan, Peter Ralph, Yuval Simons, Leo Speidel and Molly Przeworski for comments on the manuscript.\r\nNational Institutes of Health GM115889 Laura Katharine Hayward Guy Sella \r\nNational Institutes of Health GM121372 Laura Katharine Hayward","type":"journal_article","file_date_updated":"2023-01-24T12:21:32Z","corr_author":"1","_id":"12157","oa":1,"intvolume":"        11","file":[{"file_id":"12363","creator":"dernst","content_type":"application/pdf","date_updated":"2023-01-24T12:21:32Z","file_name":"2022_eLife_Hayward.pdf","file_size":18935612,"relation":"main_file","access_level":"open_access","success":1,"checksum":"28de155b231ac1c8d4501c98b2fb359a","date_created":"2023-01-24T12:21:32Z"}],"ddc":["570"],"has_accepted_license":"1","publication":"eLife","language":[{"iso":"eng"}],"scopus_import":"1","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"status":"public","date_created":"2023-01-12T12:09:00Z","title":"Polygenic adaptation after a sudden change in environment","article_number":"66697","isi":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"date_updated":"2024-10-09T21:03:38Z","month":"09","department":[{"_id":"NiBa"}],"publication_status":"published","article_processing_charge":"No","publisher":"eLife Sciences Publications","publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/elife.66697","date_published":"2022-09-26T00:00:00Z","year":"2022","citation":{"short":"L. Hayward, G. Sella, ELife 11 (2022).","apa":"Hayward, L., &#38; Sella, G. (2022). Polygenic adaptation after a sudden change in environment. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.66697\">https://doi.org/10.7554/elife.66697</a>","ama":"Hayward L, Sella G. Polygenic adaptation after a sudden change in environment. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.66697\">10.7554/elife.66697</a>","chicago":"Hayward, Laura, and Guy Sella. “Polygenic Adaptation after a Sudden Change in Environment.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.66697\">https://doi.org/10.7554/elife.66697</a>.","ista":"Hayward L, Sella G. 2022. Polygenic adaptation after a sudden change in environment. eLife. 11, 66697.","ieee":"L. Hayward and G. Sella, “Polygenic adaptation after a sudden change in environment,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","mla":"Hayward, Laura, and Guy Sella. “Polygenic Adaptation after a Sudden Change in Environment.” <i>ELife</i>, vol. 11, 66697, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.66697\">10.7554/elife.66697</a>."},"abstract":[{"text":"Polygenic adaptation is thought to be ubiquitous, yet remains poorly understood. Here, we model this process analytically, in the plausible setting of a highly polygenic, quantitative trait that experiences a sudden shift in the fitness optimum. We show how the mean phenotype changes over time, depending on the effect sizes of loci that contribute to variance in the trait, and characterize the allele dynamics at these loci. Notably, we describe the two phases of the allele dynamics: The first is a rapid phase, in which directional selection introduces small frequency differences between alleles whose effects are aligned with or opposed to the shift, ultimately leading to small differences in their probability of fixation during a second, longer phase, governed by stabilizing selection. As we discuss, key results should hold in more general settings and have important implications for efforts to identify the genetic basis of adaptation in humans and other species.","lang":"eng"}],"article_type":"original","external_id":{"isi":["000890735600001"]},"quality_controlled":"1","oa_version":"Published Version","day":"26","volume":11},{"article_type":"original","abstract":[{"lang":"eng","text":"Amyloid formation is linked to devastating neurodegenerative diseases, motivating detailed studies of the mechanisms of amyloid formation. For Aβ, the peptide associated with Alzheimer’s disease, the mechanism and rate of aggregation have been established for a range of variants and conditions <jats:italic>in vitro</jats:italic> and in bodily fluids. A key outstanding question is how the relative stabilities of monomers, fibrils and intermediates affect each step in the fibril formation process. By monitoring the kinetics of aggregation of Aβ42, in the presence of urea or guanidinium hydrochloride (GuHCl), we here determine the rates of the underlying microscopic steps and establish the importance of changes in relative stability induced by the presence of denaturant for each individual step. Denaturants shift the equilibrium towards the unfolded state of each species. We find that a non-ionic denaturant, urea, reduces the overall aggregation rate, and that the effect on nucleation is stronger than the effect on elongation. Urea reduces the rate of secondary nucleation by decreasing the coverage of fibril surfaces and the rate of nucleus formation. It also reduces the rate of primary nucleation, increasing its reaction order. The ionic denaturant, GuHCl, accelerates the aggregation at low denaturant concentrations and decelerates the aggregation at high denaturant concentrations. Below approximately 0.25 M GuHCl, the screening of repulsive electrostatic interactions between peptides by the charged denaturant dominates, leading to an increased aggregation rate. At higher GuHCl concentrations, the electrostatic repulsion is completely screened, and the denaturing effect dominates. The results illustrate how the differential effects of denaturants on stability of monomer, oligomer and fibril translate to differential effects on microscopic steps, with the rate of nucleation being most strongly reduced."}],"external_id":{"isi":["000866287100001"]},"quality_controlled":"1","day":"20","oa_version":"Published Version","volume":16,"article_number":"943355","isi":1,"title":"Influence of denaturants on amyloid β42 aggregation kinetics","month":"09","department":[{"_id":"AnSa"}],"date_updated":"2023-08-04T09:48:56Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"doi":"10.3389/fnins.2022.943355","publication_identifier":{"issn":["1662-453X"]},"publisher":"Frontiers Media","article_processing_charge":"No","publication_status":"published","citation":{"short":"T. Weiffert, G. Meisl, S. Curk, R. Cukalevski, A. Šarić, T.P.J. Knowles, S. Linse, Frontiers in Neuroscience 16 (2022).","apa":"Weiffert, T., Meisl, G., Curk, S., Cukalevski, R., Šarić, A., Knowles, T. P. J., &#38; Linse, S. (2022). Influence of denaturants on amyloid β42 aggregation kinetics. <i>Frontiers in Neuroscience</i>. Frontiers Media. <a href=\"https://doi.org/10.3389/fnins.2022.943355\">https://doi.org/10.3389/fnins.2022.943355</a>","ama":"Weiffert T, Meisl G, Curk S, et al. Influence of denaturants on amyloid β42 aggregation kinetics. <i>Frontiers in Neuroscience</i>. 2022;16. doi:<a href=\"https://doi.org/10.3389/fnins.2022.943355\">10.3389/fnins.2022.943355</a>","chicago":"Weiffert, Tanja, Georg Meisl, Samo Curk, Risto Cukalevski, Anđela Šarić, Tuomas P. J. Knowles, and Sara Linse. “Influence of Denaturants on Amyloid Β42 Aggregation Kinetics.” <i>Frontiers in Neuroscience</i>. Frontiers Media, 2022. <a href=\"https://doi.org/10.3389/fnins.2022.943355\">https://doi.org/10.3389/fnins.2022.943355</a>.","ista":"Weiffert T, Meisl G, Curk S, Cukalevski R, Šarić A, Knowles TPJ, Linse S. 2022. Influence of denaturants on amyloid β42 aggregation kinetics. Frontiers in Neuroscience. 16, 943355.","ieee":"T. Weiffert <i>et al.</i>, “Influence of denaturants on amyloid β42 aggregation kinetics,” <i>Frontiers in Neuroscience</i>, vol. 16. Frontiers Media, 2022.","mla":"Weiffert, Tanja, et al. “Influence of Denaturants on Amyloid Β42 Aggregation Kinetics.” <i>Frontiers in Neuroscience</i>, vol. 16, 943355, Frontiers Media, 2022, doi:<a href=\"https://doi.org/10.3389/fnins.2022.943355\">10.3389/fnins.2022.943355</a>."},"year":"2022","date_published":"2022-09-20T00:00:00Z","intvolume":"        16","ddc":["570"],"file":[{"creator":"dernst","file_id":"12442","file_name":"2022_FrontiersNeuroscience_Weiffert2.pdf","date_updated":"2023-01-30T09:15:13Z","content_type":"application/pdf","success":1,"access_level":"open_access","relation":"main_file","file_size":19798610,"date_created":"2023-01-30T09:15:13Z","checksum":"e67d16113ffb4fb4fa38a183d169f210"}],"language":[{"iso":"eng"}],"publication":"Frontiers in Neuroscience","has_accepted_license":"1","scopus_import":"1","date_created":"2023-01-16T09:56:43Z","status":"public","keyword":["General Neuroscience"],"type":"journal_article","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","acknowledgement":"This work was supported by grants from the Swedish Research Council (grant no. 2015-00143) and the European Research Council (grant no. 340890).","author":[{"first_name":"Tanja","full_name":"Weiffert, Tanja","last_name":"Weiffert"},{"first_name":"Georg","full_name":"Meisl, Georg","last_name":"Meisl"},{"first_name":"Samo","full_name":"Curk, Samo","last_name":"Curk"},{"first_name":"Risto","full_name":"Cukalevski, Risto","last_name":"Cukalevski"},{"last_name":"Šarić","full_name":"Šarić, Anđela","id":"bf63d406-f056-11eb-b41d-f263a6566d8b","first_name":"Anđela","orcid":"0000-0002-7854-2139"},{"first_name":"Tuomas P. J.","last_name":"Knowles","full_name":"Knowles, Tuomas P. J."},{"last_name":"Linse","full_name":"Linse, Sara","first_name":"Sara"}],"file_date_updated":"2023-01-30T09:15:13Z","_id":"12251","oa":1},{"oa_version":"Published Version","day":"15","volume":11,"ec_funded":1,"project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692"},{"call_identifier":"H2020","_id":"2634E9D2-B435-11E9-9278-68D0E5697425","name":"Circuits of Visual Attention","grant_number":"756502"},{"name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"grant_number":"LT000256","name":"Neuronal networks of salience and spatial detection in the murine superior colliculus","_id":"266D407A-B435-11E9-9278-68D0E5697425"},{"grant_number":"ALTF 1098-2017","name":"Connecting sensory with motor processing in the superior colliculus","_id":"264FEA02-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","external_id":{"isi":["000892204300001"],"pmid":["36040301"]},"abstract":[{"lang":"eng","text":"To understand the function of neuronal circuits, it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low throughput, low selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the mouse hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo."}],"article_type":"original","citation":{"mla":"Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>, vol. 11, 79848, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.79848\">10.7554/elife.79848</a>.","ieee":"A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","ista":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 11, 79848.","chicago":"Sumser, Anton L, Maximilian A Jösch, Peter M Jonas, and Yoav Ben Simon. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.79848\">https://doi.org/10.7554/elife.79848</a>.","ama":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.79848\">10.7554/elife.79848</a>","apa":"Sumser, A. L., Jösch, M. A., Jonas, P. M., &#38; Ben Simon, Y. (2022). Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.79848\">https://doi.org/10.7554/elife.79848</a>","short":"A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022)."},"year":"2022","date_published":"2022-09-15T00:00:00Z","publication_status":"published","doi":"10.7554/elife.79848","publisher":"eLife Sciences Publications","article_processing_charge":"No","publication_identifier":{"eissn":["2050-084X"]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"department":[{"_id":"MaJö"},{"_id":"PeJo"}],"month":"09","date_updated":"2025-04-15T08:29:05Z","title":"Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling","isi":1,"article_number":"79848","scopus_import":"1","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"status":"public","date_created":"2023-01-16T10:04:15Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"has_accepted_license":"1","language":[{"iso":"eng"}],"publication":"eLife","file":[{"file_id":"12463","creator":"dernst","content_type":"application/pdf","file_name":"2022_eLife_Sumser.pdf","date_updated":"2023-01-30T11:50:53Z","relation":"main_file","file_size":8506811,"access_level":"open_access","success":1,"checksum":"5a2a65e3e7225090c3d8199f3bbd7b7b","date_created":"2023-01-30T11:50:53Z"}],"ddc":["570"],"intvolume":"        11","pmid":1,"oa":1,"_id":"12288","file_date_updated":"2023-01-30T11:50:53Z","corr_author":"1","type":"journal_article","author":[{"orcid":"0000-0002-4792-1881","first_name":"Anton L","last_name":"Sumser","full_name":"Sumser, Anton L","id":"3320A096-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-3937-1330","first_name":"Maximilian A","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","full_name":"Jösch, Maximilian A","last_name":"Jösch"},{"last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","first_name":"Peter M","orcid":"0000-0001-5001-4804"},{"full_name":"Ben Simon, Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","last_name":"Ben Simon","first_name":"Yoav"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","acknowledgement":"We thank F Marr for technical assistance, A Murray for RVdG-CVS-N2c viruses and Neuro2A packaging cell-lines and J Watson for reading the manuscript. This research was supported by the Scientific Service Units (SSU) of IST-Austria through resources provided by the Imaging and Optics Facility (IOF) and the Preclinical Facility (PCF). This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC advanced grant No 692692, PJ, ERC starting grant No 756502, MJ), the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, PJ), the Human Frontier Science Program (LT000256/2018-L, AS) and EMBO (ALTF 1098-2017, AS)."},{"file":[{"creator":"dernst","file_id":"11454","content_type":"application/pdf","file_name":"2022_eLife_Somermeyer.pdf","date_updated":"2022-06-20T07:44:19Z","file_size":5297213,"relation":"main_file","success":1,"access_level":"open_access","checksum":"7573c28f44028ab0cc81faef30039e44","date_created":"2022-06-20T07:44:19Z"}],"ddc":["570"],"pmid":1,"intvolume":"        11","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"date_created":"2022-06-18T09:06:59Z","status":"public","scopus_import":"1","has_accepted_license":"1","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"language":[{"iso":"eng"}],"publication":"eLife","file_date_updated":"2022-06-20T07:44:19Z","corr_author":"1","type":"journal_article","author":[{"full_name":"Gonzalez Somermeyer, Louisa","id":"4720D23C-F248-11E8-B48F-1D18A9856A87","last_name":"Gonzalez Somermeyer","orcid":"0000-0001-9139-5383","first_name":"Louisa"},{"first_name":"Aubin","full_name":"Fleiss, Aubin","last_name":"Fleiss"},{"first_name":"Alexander S","last_name":"Mishin","full_name":"Mishin, Alexander S"},{"first_name":"Nina G","last_name":"Bozhanova","full_name":"Bozhanova, Nina G"},{"first_name":"Anna A","last_name":"Igolkina","full_name":"Igolkina, Anna A"},{"first_name":"Jens","full_name":"Meiler, Jens","last_name":"Meiler"},{"last_name":"Alaball Pujol","full_name":"Alaball Pujol, Maria-Elisenda","first_name":"Maria-Elisenda"},{"full_name":"Putintseva, Ekaterina V","last_name":"Putintseva","first_name":"Ekaterina V"},{"first_name":"Karen S","last_name":"Sarkisyan","full_name":"Sarkisyan, Karen S"},{"last_name":"Kondrashov","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","full_name":"Kondrashov, Fyodor","first_name":"Fyodor","orcid":"0000-0001-8243-4694"}],"acknowledgement":"We thank Ondřej Draganov, Rodrigo Redondo, Bor Kavčič, Mia Juračić and Andrea Pauli for discussion and technical advice. We thank Anita Testa Salmazo for advice on resin protein purification, Dmitry Bolotin and the Milaboratory (milaboratory.com) for access to computing and storage infrastructure, and Josef Houser and Eva Fujdiarova for technical assistance and data interpretation. Core facility Biomolecular Interactions and Crystallization of CEITEC Masaryk University is gratefully acknowledged for the obtaining of the scientific data presented in this paper. This research was supported by the Scientific Service Units (SSU) of IST-Austria\r\nthrough resources provided by the Bioimaging Facility (BIF), and the Life Science Facility (LSF). MiSeq and HiSeq NGS sequencing was performed by the Next Generation Sequencing Facility at Vienna BioCenter Core Facilities (VBCF), member of the Vienna BioCenter (VBC), Austria. FACS was performed at the BioOptics Facility of the Institute of Molecular Pathology (IMP), Austria. We also thank the Biomolecular Crystallography Facility in the Vanderbilt University Center for Structural Biology. We are grateful to Joel M Harp for help with X-ray data collection. This work was supported by the ERC Consolidator grant to FAK (771209—CharFL). KSS acknowledges support by President’s Grant МК–5405.2021.1.4, the Imperial College Research Fellowship and the MRC London Institute of Medical Sciences (UKRI MC-A658-5QEA0).\r\nAF is supported by the Marie Skłodowska-Curie Fellowship (H2020-MSCA-IF-2019, Grant Agreement No. 898203, Project acronym \"FLINDIP\"). Experiments were partially carried out using equipment provided by the Institute of Bioorganic Chemistry of the Russian Academy of Sciences Сore Facility (CKP IBCH). This work was supported by a Russian Science Foundation grant 19-74-10102.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 665,385.","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"related_material":{"link":[{"relation":"software","url":"https://github.com/aequorea238/Orthologous_GFP_Fitness_Peaks"}],"record":[{"id":"17850","status":"public","relation":"dissertation_contains"}]},"_id":"11448","abstract":[{"text":"Studies of protein fitness landscapes reveal biophysical constraints guiding protein evolution and empower prediction of functional proteins. However, generalisation of these findings is limited due to scarceness of systematic data on fitness landscapes of proteins with a defined evolutionary relationship. We characterized the fitness peaks of four orthologous fluorescent proteins with a broad range of sequence divergence. While two of the four studied fitness peaks were sharp, the other two were considerably flatter, being almost entirely free of epistatic interactions. Mutationally robust proteins, characterized by a flat fitness peak, were not optimal templates for machine-learning-driven protein design – instead, predictions were more accurate for fragile proteins with epistatic landscapes. Our work paves insights for practical application of fitness landscape heterogeneity in protein engineering.","lang":"eng"}],"article_type":"original","volume":11,"oa_version":"Published Version","day":"05","ec_funded":1,"project":[{"_id":"26580278-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Characterizing the fitness landscape on population and global scales","grant_number":"771209"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"International IST Doctoral Program","grant_number":"665385"}],"quality_controlled":"1","external_id":{"pmid":["35510622"],"isi":["000799197200001"]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"month":"05","department":[{"_id":"GradSch"},{"_id":"FyKo"}],"date_updated":"2026-04-07T13:25:01Z","title":"Heterogeneity of the GFP fitness landscape and data-driven protein design","article_number":"75842","isi":1,"citation":{"short":"L. Gonzalez Somermeyer, A. Fleiss, A.S. Mishin, N.G. Bozhanova, A.A. Igolkina, J. Meiler, M.-E. Alaball Pujol, E.V. Putintseva, K.S. Sarkisyan, F. Kondrashov, ELife 11 (2022).","apa":"Gonzalez Somermeyer, L., Fleiss, A., Mishin, A. S., Bozhanova, N. G., Igolkina, A. A., Meiler, J., … Kondrashov, F. (2022). Heterogeneity of the GFP fitness landscape and data-driven protein design. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.75842\">https://doi.org/10.7554/elife.75842</a>","ama":"Gonzalez Somermeyer L, Fleiss A, Mishin AS, et al. Heterogeneity of the GFP fitness landscape and data-driven protein design. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.75842\">10.7554/elife.75842</a>","chicago":"Gonzalez Somermeyer, Louisa, Aubin Fleiss, Alexander S Mishin, Nina G Bozhanova, Anna A Igolkina, Jens Meiler, Maria-Elisenda Alaball Pujol, Ekaterina V Putintseva, Karen S Sarkisyan, and Fyodor Kondrashov. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.75842\">https://doi.org/10.7554/elife.75842</a>.","ista":"Gonzalez Somermeyer L, Fleiss A, Mishin AS, Bozhanova NG, Igolkina AA, Meiler J, Alaball Pujol M-E, Putintseva EV, Sarkisyan KS, Kondrashov F. 2022. Heterogeneity of the GFP fitness landscape and data-driven protein design. eLife. 11, 75842.","ieee":"L. Gonzalez Somermeyer <i>et al.</i>, “Heterogeneity of the GFP fitness landscape and data-driven protein design,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","mla":"Gonzalez Somermeyer, Louisa, et al. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” <i>ELife</i>, vol. 11, 75842, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.75842\">10.7554/elife.75842</a>."},"date_published":"2022-05-05T00:00:00Z","year":"2022","publication_status":"published","doi":"10.7554/elife.75842","publication_identifier":{"issn":["2050-084X"]},"article_processing_charge":"No","publisher":"eLife Sciences Publications"},{"date_created":"2022-06-17T16:16:15Z","scopus_import":"1","keyword":["Computational Theory and Mathematics","General Agricultural and Biological Sciences","Pharmacology","General Environmental Science","General Biochemistry","Genetics and Molecular Biology","General Mathematics","Immunology","General Neuroscience"],"status":"public","publication":"Bulletin of Mathematical Biology","language":[{"iso":"eng"}],"has_accepted_license":"1","ddc":["510","570"],"file":[{"creator":"dernst","file_id":"11455","date_updated":"2022-06-20T07:51:32Z","file_name":"2022_BulletinMathBiology_Saona.pdf","content_type":"application/pdf","success":1,"access_level":"open_access","file_size":463025,"relation":"main_file","date_created":"2022-06-20T07:51:32Z","checksum":"05a1fe7d10914a00c2bca9b447993a65"}],"pmid":1,"intvolume":"        84","oa":1,"related_material":{"link":[{"url":"https://doi.org/10.1007/s11538-022-01118-z","relation":"erratum"}]},"_id":"11447","corr_author":"1","issue":"8","file_date_updated":"2022-06-20T07:51:32Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledgement":"We are grateful to Herbert Edelsbrunner and Jeferson Zapata for helpful discussions. Open access funding provided by Austrian Science Fund (FWF). Partially supported by the ERC Consolidator (771209–CharFL) and the FWF Austrian Science Fund (I5127-B) grants to FAK.","author":[{"full_name":"Saona Urmeneta, Raimundo J","id":"BD1DF4C4-D767-11E9-B658-BC13E6697425","last_name":"Saona Urmeneta","first_name":"Raimundo J","orcid":"0000-0001-5103-038X"},{"orcid":"0000-0001-8243-4694","first_name":"Fyodor","last_name":"Kondrashov","full_name":"Kondrashov, Fyodor","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-6246-1465","first_name":"Kseniia","id":"4E6DC800-AE37-11E9-AC72-31CAE5697425","full_name":"Khudiakova, Kseniia","last_name":"Khudiakova"}],"type":"journal_article","ec_funded":1,"volume":84,"day":"17","oa_version":"Published Version","quality_controlled":"1","external_id":{"isi":["000812509800001"],"pmid":["35713756"]},"project":[{"_id":"26580278-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Characterizing the fitness landscape on population and global scales","grant_number":"771209"},{"grant_number":"I05127","name":"Evolutionary analysis of gene regulation","_id":"34e076d6-11ca-11ed-8bc3-aec76c41a181"}],"article_type":"original","abstract":[{"text":"Empirical essays of fitness landscapes suggest that they may be rugged, that is having multiple fitness peaks. Such fitness landscapes, those that have multiple peaks, necessarily have special local structures, called reciprocal sign epistasis (Poelwijk et al. in J Theor Biol 272:141–144, 2011). Here, we investigate the quantitative relationship between the number of fitness peaks and the number of reciprocal sign epistatic interactions. Previously, it has been shown (Poelwijk et al. in J Theor Biol 272:141–144, 2011) that pairwise reciprocal sign epistasis is a necessary but not sufficient condition for the existence of multiple peaks. Applying discrete Morse theory, which to our knowledge has never been used in this context, we extend this result by giving the minimal number of reciprocal sign epistatic interactions required to create a given number of peaks.","lang":"eng"}],"date_published":"2022-06-17T00:00:00Z","year":"2022","citation":{"apa":"Saona Urmeneta, R. J., Kondrashov, F., &#38; Khudiakova, K. (2022). Relation between the number of peaks and the number of reciprocal sign epistatic interactions. <i>Bulletin of Mathematical Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1007/s11538-022-01029-z\">https://doi.org/10.1007/s11538-022-01029-z</a>","short":"R.J. Saona Urmeneta, F. Kondrashov, K. Khudiakova, Bulletin of Mathematical Biology 84 (2022).","chicago":"Saona Urmeneta, Raimundo J, Fyodor Kondrashov, and Kseniia Khudiakova. “Relation between the Number of Peaks and the Number of Reciprocal Sign Epistatic Interactions.” <i>Bulletin of Mathematical Biology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1007/s11538-022-01029-z\">https://doi.org/10.1007/s11538-022-01029-z</a>.","ama":"Saona Urmeneta RJ, Kondrashov F, Khudiakova K. Relation between the number of peaks and the number of reciprocal sign epistatic interactions. <i>Bulletin of Mathematical Biology</i>. 2022;84(8). doi:<a href=\"https://doi.org/10.1007/s11538-022-01029-z\">10.1007/s11538-022-01029-z</a>","ista":"Saona Urmeneta RJ, Kondrashov F, Khudiakova K. 2022. Relation between the number of peaks and the number of reciprocal sign epistatic interactions. Bulletin of Mathematical Biology. 84(8), 74.","mla":"Saona Urmeneta, Raimundo J., et al. “Relation between the Number of Peaks and the Number of Reciprocal Sign Epistatic Interactions.” <i>Bulletin of Mathematical Biology</i>, vol. 84, no. 8, 74, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1007/s11538-022-01029-z\">10.1007/s11538-022-01029-z</a>.","ieee":"R. J. Saona Urmeneta, F. Kondrashov, and K. Khudiakova, “Relation between the number of peaks and the number of reciprocal sign epistatic interactions,” <i>Bulletin of Mathematical Biology</i>, vol. 84, no. 8. Springer Nature, 2022."},"publication_identifier":{"issn":["0092-8240"],"eissn":["1522-9602"]},"article_processing_charge":"Yes (via OA deal)","publisher":"Springer Nature","doi":"10.1007/s11538-022-01029-z","publication_status":"published","date_updated":"2026-04-15T08:51:10Z","month":"06","department":[{"_id":"GradSch"},{"_id":"NiBa"},{"_id":"JaMa"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_number":"74","isi":1,"title":"Relation between the number of peaks and the number of reciprocal sign epistatic interactions"},{"project":[{"grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020"},{"grant_number":"715571","call_identifier":"H2020","_id":"25D4A630-B435-11E9-9278-68D0E5697425","name":"Microglia action towards neuronal circuit formation and function in health and disease"}],"quality_controlled":"1","external_id":{"pmid":["36180790"],"isi":["000862214700001"]},"ec_funded":1,"day":"01","volume":25,"oa_version":"Published Version","article_type":"original","abstract":[{"lang":"eng","text":"Environmental cues influence the highly dynamic morphology of microglia. Strategies to characterize these changes usually involve user-selected morphometric features, which preclude the identification of a spectrum of context-dependent morphological phenotypes. Here we develop MorphOMICs, a topological data analysis approach, which enables semiautomatic mapping of microglial morphology into an atlas of cue-dependent phenotypes and overcomes feature-selection biases and biological variability. We extract spatially heterogeneous and sexually dimorphic morphological phenotypes for seven adult mouse brain regions. This sex-specific phenotype declines with maturation but increases over the disease trajectories in two neurodegeneration mouse models, with females showing a faster morphological shift in affected brain regions. Remarkably, microglia morphologies reflect an adaptation upon repeated exposure to ketamine anesthesia and do not recover to control morphologies. Finally, we demonstrate that both long primary processes and short terminal processes provide distinct insights to morphological phenotypes. MorphOMICs opens a new perspective to characterize microglial morphology."}],"doi":"10.1038/s41593-022-01167-6","publisher":"Springer Nature","publication_identifier":{"eissn":["1546-1726"],"issn":["1097-6256"]},"article_processing_charge":"No","publication_status":"published","citation":{"chicago":"Colombo, Gloria, Ryan J Cubero, Lida Kanari, Alessandro Venturino, Rouven Schulz, Martina Scolamiero, Jens Agerberg, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” <i>Nature Neuroscience</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41593-022-01167-6\">https://doi.org/10.1038/s41593-022-01167-6</a>.","ama":"Colombo G, Cubero RJ, Kanari L, et al. A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. <i>Nature Neuroscience</i>. 2022;25(10):1379-1393. doi:<a href=\"https://doi.org/10.1038/s41593-022-01167-6\">10.1038/s41593-022-01167-6</a>","apa":"Colombo, G., Cubero, R. J., Kanari, L., Venturino, A., Schulz, R., Scolamiero, M., … Siegert, S. (2022). A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. <i>Nature Neuroscience</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41593-022-01167-6\">https://doi.org/10.1038/s41593-022-01167-6</a>","short":"G. Colombo, R.J. Cubero, L. Kanari, A. Venturino, R. Schulz, M. Scolamiero, J. Agerberg, H. Mathys, L.-H. Tsai, W. Chachólski, K. Hess, S. Siegert, Nature Neuroscience 25 (2022) 1379–1393.","mla":"Colombo, Gloria, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” <i>Nature Neuroscience</i>, vol. 25, no. 10, Springer Nature, 2022, pp. 1379–93, doi:<a href=\"https://doi.org/10.1038/s41593-022-01167-6\">10.1038/s41593-022-01167-6</a>.","ieee":"G. Colombo <i>et al.</i>, “A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes,” <i>Nature Neuroscience</i>, vol. 25, no. 10. Springer Nature, pp. 1379–1393, 2022.","ista":"Colombo G, Cubero RJ, Kanari L, Venturino A, Schulz R, Scolamiero M, Agerberg J, Mathys H, Tsai L-H, Chachólski W, Hess K, Siegert S. 2022. A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. Nature Neuroscience. 25(10), 1379–1393."},"date_published":"2022-10-01T00:00:00Z","year":"2022","isi":1,"title":"A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes","department":[{"_id":"SaSi"}],"month":"10","date_updated":"2026-04-22T22:30:37Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"language":[{"iso":"eng"}],"publication":"Nature Neuroscience","has_accepted_license":"1","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"ScienComp"}],"date_created":"2023-01-16T09:53:07Z","scopus_import":"1","status":"public","keyword":["General Neuroscience"],"intvolume":"        25","pmid":1,"page":"1379-1393","ddc":["570"],"file":[{"checksum":"28431146873096f52e0107b534f178c9","date_created":"2023-01-30T08:06:56Z","relation":"main_file","file_size":23789835,"success":1,"access_level":"open_access","content_type":"application/pdf","date_updated":"2023-01-30T08:06:56Z","file_name":"2022_NatureNeuroscience_Colombo.pdf","creator":"dernst","file_id":"12437"}],"_id":"12244","oa":1,"related_material":{"link":[{"url":"https://ista.ac.at/en/news/morphomics-revealing-the-hidden-meaning-of-microglia-shape/","description":"News on ISTA website","relation":"press_release"}],"record":[{"id":"12378","status":"public","relation":"dissertation_contains"}]},"type":"journal_article","author":[{"orcid":"0000-0001-9434-8902","first_name":"Gloria","last_name":"Colombo","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","full_name":"Colombo, Gloria"},{"first_name":"Ryan J","orcid":"0000-0003-0002-1867","full_name":"Cubero, Ryan J","id":"850B2E12-9CD4-11E9-837F-E719E6697425","last_name":"Cubero"},{"first_name":"Lida","last_name":"Kanari","full_name":"Kanari, Lida"},{"orcid":"0000-0003-2356-9403","first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","full_name":"Venturino, Alessandro","last_name":"Venturino"},{"orcid":"0000-0001-5297-733X","first_name":"Rouven","last_name":"Schulz","full_name":"Schulz, Rouven","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Scolamiero, Martina","last_name":"Scolamiero","first_name":"Martina"},{"first_name":"Jens","full_name":"Agerberg, Jens","last_name":"Agerberg"},{"first_name":"Hansruedi","full_name":"Mathys, Hansruedi","last_name":"Mathys"},{"first_name":"Li-Huei","full_name":"Tsai, Li-Huei","last_name":"Tsai"},{"first_name":"Wojciech","full_name":"Chachólski, Wojciech","last_name":"Chachólski"},{"first_name":"Kathryn","full_name":"Hess, Kathryn","last_name":"Hess"},{"first_name":"Sandra","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","acknowledgement":"We thank the scientific service units at ISTA, in particular M. Schunn’s team at the preclinical facility, and especially our colony manager S. Haslinger, for excellent support. We are also grateful to the ISTA Imaging & Optics Facility, and in particular C. Sommer for helping with the data file conversions. We thank R. Erhart from the ISTA Scientific Computing Unit for improving the script performance. We thank M. Maes, B. Nagy, S. Oakeley and M. Benevento and all members of the Siegert group for constant feedback on the project and on the manuscript. This research was supported by the European Union Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Actions program (754411 to R.J.A.C.), and by the European Research Council (grant no. 715571 to S.S.). L.K. was supported by funding to the Blue Brain Project, a research center of the École polytechnique fédérale de Lausanne, from the Swiss government’s ETH Board of the Swiss Federal Institutes of Technology. L.-H.T. was supported by NIH (grant no. R37NS051874) and by the JPB Foundation. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.","issue":"10","corr_author":"1","file_date_updated":"2023-01-30T08:06:56Z"},{"year":"2021","date_published":"2021-12-01T00:00:00Z","citation":{"short":"T. Bian, R. Klajn, Annals of the New York Academy of Sciences 1505 (2021) 191–201.","apa":"Bian, T., &#38; Klajn, R. (2021). Morphology control in crystalline nanoparticle–polymer aggregates. <i>Annals of the New York Academy of Sciences</i>. Wiley. <a href=\"https://doi.org/10.1111/nyas.14674\">https://doi.org/10.1111/nyas.14674</a>","ama":"Bian T, Klajn R. Morphology control in crystalline nanoparticle–polymer aggregates. <i>Annals of the New York Academy of Sciences</i>. 2021;1505(1):191-201. doi:<a href=\"https://doi.org/10.1111/nyas.14674\">10.1111/nyas.14674</a>","chicago":"Bian, Tong, and Rafal Klajn. “Morphology Control in Crystalline Nanoparticle–Polymer Aggregates.” <i>Annals of the New York Academy of Sciences</i>. Wiley, 2021. <a href=\"https://doi.org/10.1111/nyas.14674\">https://doi.org/10.1111/nyas.14674</a>.","ista":"Bian T, Klajn R. 2021. Morphology control in crystalline nanoparticle–polymer aggregates. Annals of the New York Academy of Sciences. 1505(1), 191–201.","ieee":"T. Bian and R. Klajn, “Morphology control in crystalline nanoparticle–polymer aggregates,” <i>Annals of the New York Academy of Sciences</i>, vol. 1505, no. 1. Wiley, pp. 191–201, 2021.","mla":"Bian, Tong, and Rafal Klajn. “Morphology Control in Crystalline Nanoparticle–Polymer Aggregates.” <i>Annals of the New York Academy of Sciences</i>, vol. 1505, no. 1, Wiley, 2021, pp. 191–201, doi:<a href=\"https://doi.org/10.1111/nyas.14674\">10.1111/nyas.14674</a>."},"publication_identifier":{"eissn":["1749-6632"],"issn":["0077-8923"]},"publisher":"Wiley","article_processing_charge":"No","doi":"10.1111/nyas.14674","publication_status":"published","date_updated":"2024-10-14T12:12:06Z","month":"12","title":"Morphology control in crystalline nanoparticle–polymer aggregates","volume":1505,"day":"01","oa_version":"Published Version","quality_controlled":"1","external_id":{"pmid":["34427923"]},"article_type":"original","abstract":[{"text":"Self-assembly of nanoparticles can be mediated by polymers, but has so far led almost exclusively to nanoparticle aggregates that are amorphous. Here, we employed Coulombic interactions to generate a range of composite materials from mixtures of charged nanoparticles and oppositely charged polymers. The assembly behavior of these nanoparticle/polymer composites depends on their order of addition: polymers added to nanoparticles give rise to stable aggregates, but nanoparticles added to polymers disassemble the initially formed aggregates. The amorphous aggregates were transformed into crystalline ones by transiently increasing the ionic strength of the solution. The morphology of the resulting crystals depended on the length of the polymer: short polymer chains mediated the self-assembly of nanoparticles into strongly faceted crystals, whereas long chains led to pseudospherical nanoparticle/polymer assemblies, within which the crystalline order of nanoparticles was retained.","lang":"eng"}],"main_file_link":[{"url":"https://doi.org/10.1111/nyas.14674","open_access":"1"}],"oa":1,"_id":"13356","issue":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"first_name":"Tong","last_name":"Bian","full_name":"Bian, Tong"},{"last_name":"Klajn","full_name":"Klajn, Rafal","id":"8e84690e-1e48-11ed-a02b-a1e6fb8bb53b","first_name":"Rafal"}],"type":"journal_article","extern":"1","scopus_import":"1","date_created":"2023-08-01T09:33:39Z","status":"public","keyword":["History and Philosophy of Science","General Biochemistry","Genetics and Molecular Biology","General Neuroscience"],"publication":"Annals of the New York Academy of Sciences","language":[{"iso":"eng"}],"ddc":["540"],"pmid":1,"page":"191-201","intvolume":"      1505"},{"day":"02","oa_version":"Published Version","volume":40,"external_id":{"pmid":["34524703"]},"quality_controlled":"1","abstract":[{"lang":"eng","text":"RNA viruses induce the formation of subcellular organelles that provide microenvironments conducive to their replication. Here we show that replication factories of rotaviruses represent protein‐RNA condensates that are formed via liquid–liquid phase separation of the viroplasm‐forming proteins NSP5 and rotavirus RNA chaperone NSP2. Upon mixing, these proteins readily form condensates at physiologically relevant low micromolar concentrations achieved in the cytoplasm of virus‐infected cells. Early infection stage condensates could be reversibly dissolved by 1,6‐hexanediol, as well as propylene glycol that released rotavirus transcripts from these condensates. During the early stages of infection, propylene glycol treatments reduced viral replication and phosphorylation of the condensate‐forming protein NSP5. During late infection, these condensates exhibited altered material properties and became resistant to propylene glycol, coinciding with hyperphosphorylation of NSP5. Some aspects of the assembly of cytoplasmic rotavirus replication factories mirror the formation of other ribonucleoprotein granules. Such viral RNA‐rich condensates that support replication of multi‐segmented genomes represent an attractive target for developing novel therapeutic approaches."}],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.15252/embj.2021107711"}],"article_type":"original","date_published":"2021-11-02T00:00:00Z","year":"2021","citation":{"ista":"Geiger F, Acker J, Papa G, Wang X, Arter WE, Saar KL, Erkamp NA, Qi R, Bravo JPK, Strauss S, Krainer G, Burrone OR, Jungmann R, Knowles TP, Engelke H, Borodavka A. 2021. Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses. The EMBO Journal. 40(21), e107711.","ieee":"F. Geiger <i>et al.</i>, “Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses,” <i>The EMBO Journal</i>, vol. 40, no. 21. Embo Press, 2021.","mla":"Geiger, Florian, et al. “Liquid–Liquid Phase Separation Underpins the Formation of Replication Factories in Rotaviruses.” <i>The EMBO Journal</i>, vol. 40, no. 21, e107711, Embo Press, 2021, doi:<a href=\"https://doi.org/10.15252/embj.2021107711\">10.15252/embj.2021107711</a>.","short":"F. Geiger, J. Acker, G. Papa, X. Wang, W.E. Arter, K.L. Saar, N.A. Erkamp, R. Qi, J.P.K. Bravo, S. Strauss, G. Krainer, O.R. Burrone, R. Jungmann, T.P. Knowles, H. Engelke, A. Borodavka, The EMBO Journal 40 (2021).","apa":"Geiger, F., Acker, J., Papa, G., Wang, X., Arter, W. E., Saar, K. L., … Borodavka, A. (2021). Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses. <i>The EMBO Journal</i>. Embo Press. <a href=\"https://doi.org/10.15252/embj.2021107711\">https://doi.org/10.15252/embj.2021107711</a>","ama":"Geiger F, Acker J, Papa G, et al. Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses. <i>The EMBO Journal</i>. 2021;40(21). doi:<a href=\"https://doi.org/10.15252/embj.2021107711\">10.15252/embj.2021107711</a>","chicago":"Geiger, Florian, Julia Acker, Guido Papa, Xinyu Wang, William E Arter, Kadi L Saar, Nadia A Erkamp, et al. “Liquid–Liquid Phase Separation Underpins the Formation of Replication Factories in Rotaviruses.” <i>The EMBO Journal</i>. Embo Press, 2021. <a href=\"https://doi.org/10.15252/embj.2021107711\">https://doi.org/10.15252/embj.2021107711</a>."},"publication_status":"published","publication_identifier":{"issn":["0261-4189"],"eissn":["1460-2075"]},"publisher":"Embo Press","article_processing_charge":"Yes","doi":"10.15252/embj.2021107711","date_updated":"2024-06-04T06:08:16Z","month":"11","title":"Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses","article_number":"e107711","date_created":"2024-03-20T10:42:39Z","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","Molecular Biology","General Neuroscience"],"scopus_import":"1","status":"public","publication":"The EMBO Journal","language":[{"iso":"eng"}],"intvolume":"        40","pmid":1,"oa":1,"_id":"15138","issue":"21","extern":"1","author":[{"full_name":"Geiger, Florian","last_name":"Geiger","first_name":"Florian"},{"full_name":"Acker, Julia","last_name":"Acker","first_name":"Julia"},{"last_name":"Papa","full_name":"Papa, Guido","first_name":"Guido"},{"full_name":"Wang, Xinyu","last_name":"Wang","first_name":"Xinyu"},{"first_name":"William E","full_name":"Arter, William E","last_name":"Arter"},{"first_name":"Kadi L","full_name":"Saar, Kadi L","last_name":"Saar"},{"first_name":"Nadia A","last_name":"Erkamp","full_name":"Erkamp, Nadia A"},{"first_name":"Runzhang","last_name":"Qi","full_name":"Qi, Runzhang"},{"first_name":"Jack Peter Kelly","orcid":"0000-0003-0456-0753","id":"96aecfa5-8931-11ee-af30-aa6a5d6eee0e","full_name":"Bravo, Jack Peter Kelly","last_name":"Bravo"},{"first_name":"Sebastian","last_name":"Strauss","full_name":"Strauss, Sebastian"},{"first_name":"Georg","full_name":"Krainer, Georg","last_name":"Krainer"},{"last_name":"Burrone","full_name":"Burrone, Oscar R","first_name":"Oscar R"},{"first_name":"Ralf","last_name":"Jungmann","full_name":"Jungmann, Ralf"},{"first_name":"Tuomas PJ","full_name":"Knowles, Tuomas PJ","last_name":"Knowles"},{"full_name":"Engelke, Hanna","last_name":"Engelke","first_name":"Hanna"},{"first_name":"Alexander","full_name":"Borodavka, Alexander","last_name":"Borodavka"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"journal_article"},{"article_number":"e63819","title":"Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse","department":[{"_id":"PeJo"}],"month":"02","date_updated":"2024-04-09T11:15:01Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"doi":"10.7554/elife.63819","publication_identifier":{"issn":["2050-084X"]},"publisher":"eLife Sciences Publications","article_processing_charge":"Yes","publication_status":"published","citation":{"short":"T.S. Balmer, C. Borges Merjane, L.O. Trussell, ELife 10 (2021).","apa":"Balmer, T. S., Borges Merjane, C., &#38; Trussell, L. O. (2021). Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.63819\">https://doi.org/10.7554/elife.63819</a>","ama":"Balmer TS, Borges Merjane C, Trussell LO. Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/elife.63819\">10.7554/elife.63819</a>","chicago":"Balmer, Timothy S, Carolina Borges Merjane, and Laurence O Trussell. “Incomplete Removal of Extracellular Glutamate Controls Synaptic Transmission and Integration at a Cerebellar Synapse.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/elife.63819\">https://doi.org/10.7554/elife.63819</a>.","ista":"Balmer TS, Borges Merjane C, Trussell LO. 2021. Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse. eLife. 10, e63819.","ieee":"T. S. Balmer, C. Borges Merjane, and L. O. Trussell, “Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","mla":"Balmer, Timothy S., et al. “Incomplete Removal of Extracellular Glutamate Controls Synaptic Transmission and Integration at a Cerebellar Synapse.” <i>ELife</i>, vol. 10, e63819, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/elife.63819\">10.7554/elife.63819</a>."},"date_published":"2021-02-22T00:00:00Z","year":"2021","article_type":"original","abstract":[{"lang":"eng","text":"Synapses of glutamatergic mossy fibers (MFs) onto cerebellar unipolar brush cells (UBCs) generate slow excitatory (ON) or inhibitory (OFF) postsynaptic responses dependent on the complement of glutamate receptors expressed on the UBC’s large dendritic brush. Using mouse brain slice recording and computational modeling of synaptic transmission, we found that substantial glutamate is maintained in the UBC synaptic cleft, sufficient to modify spontaneous firing in OFF UBCs and tonically desensitize AMPARs of ON UBCs. The source of this ambient glutamate was spontaneous, spike-independent exocytosis from the MF terminal, and its level was dependent on activity of glutamate transporters EAAT1–2. Increasing levels of ambient glutamate shifted the polarity of evoked synaptic responses in ON UBCs and altered the phase of responses to in vivo-like synaptic activity. Unlike classical fast synapses, receptors at the UBC synapse are virtually always exposed to a significant level of glutamate, which varies in a graded manner during transmission."}],"quality_controlled":"1","external_id":{"pmid":["33616036"]},"volume":10,"day":"22","oa_version":"Published Version","type":"journal_article","author":[{"last_name":"Balmer","full_name":"Balmer, Timothy S","first_name":"Timothy S"},{"last_name":"Borges Merjane","full_name":"Borges Merjane, Carolina","id":"4305C450-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0005-401X","first_name":"Carolina"},{"full_name":"Trussell, Laurence O","last_name":"Trussell","first_name":"Laurence O"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file_date_updated":"2024-04-09T11:13:07Z","_id":"15273","oa":1,"pmid":1,"intvolume":"        10","ddc":["570"],"file":[{"content_type":"application/pdf","file_name":"2021_eLife_Balmer.pdf","date_updated":"2024-04-09T11:13:07Z","file_id":"15307","creator":"dernst","checksum":"bbd4de2e54b7fbc11fba14f59e87fe3f","date_created":"2024-04-09T11:13:07Z","relation":"main_file","file_size":6997954,"access_level":"open_access","success":1}],"language":[{"iso":"eng"}],"publication":"eLife","has_accepted_license":"1","status":"public","date_created":"2024-04-03T07:58:11Z","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"]},{"date_published":"2021-11-17T00:00:00Z","year":"2021","citation":{"mla":"Conde-Dusman, María J., et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” <i>ELife</i>, vol. 10, e71575, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/elife.71575\">10.7554/elife.71575</a>.","ieee":"M. J. Conde-Dusman <i>et al.</i>, “Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","ista":"Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, Garcia Rabaneda LE, García-Lira C, Grand T, Briz V, Velasco ER, Andero Galí R, Niñerola S, Barco A, Paoletti P, Wesseling JF, Gardoni F, Tavalin SJ, Perez-Otaño I. 2021. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife. 10, e71575.","chicago":"Conde-Dusman, María J, Partha N Dey, Óscar Elía-Zudaire, Luis E Garcia Rabaneda, Carmen García-Lira, Teddy Grand, Victor Briz, et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/elife.71575\">https://doi.org/10.7554/elife.71575</a>.","ama":"Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, et al. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/elife.71575\">10.7554/elife.71575</a>","apa":"Conde-Dusman, M. J., Dey, P. N., Elía-Zudaire, Ó., Garcia Rabaneda, L. E., García-Lira, C., Grand, T., … Perez-Otaño, I. (2021). Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.71575\">https://doi.org/10.7554/elife.71575</a>","short":"M.J. Conde-Dusman, P.N. Dey, Ó. Elía-Zudaire, L.E. Garcia Rabaneda, C. García-Lira, T. Grand, V. Briz, E.R. Velasco, R. Andero Galí, S. Niñerola, A. Barco, P. Paoletti, J.F. Wesseling, F. Gardoni, S.J. Tavalin, I. Perez-Otaño, ELife 10 (2021)."},"publication_identifier":{"issn":["2050-084X"]},"article_processing_charge":"No","publisher":"eLife Sciences Publications","doi":"10.7554/elife.71575","publication_status":"published","date_updated":"2024-10-21T06:02:05Z","month":"11","department":[{"_id":"GaNo"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_number":"e71575","isi":1,"title":"Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly","day":"17","oa_version":"Published Version","volume":10,"external_id":{"isi":["000720945900001"]},"quality_controlled":"1","article_type":"original","abstract":[{"lang":"eng","text":"De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement."}],"oa":1,"_id":"10301","file_date_updated":"2021-11-18T07:02:02Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","acknowledgement":"We thank Stuart Lipton and Nobuki Nakanishi for providing the Grin3a knockout mice, Beverly Davidson for the AAV-caRheb, Jose Esteban for help with behavioral and biochemical experiments, and Noelia Campillo, Rebeca Martínez-Turrillas, and Ana Navarro for expert technical help. Work was funded by the UTE project CIMA; fellowships from the Fundación Tatiana Pérez de Guzmán el Bueno, FEBS, and IBRO (to M.J.C.D.), Generalitat Valenciana (to O.E.-Z.), Juan de la Cierva (to L.G.R.), FPI-MINECO (to E.R.V., to S.N.) and Intertalentum postdoctoral program (to V.B.); ANR (GluBrain3A) and ERC Advanced Grants (#693021) (to P.P.); Ramón y Cajal program RYC2014-15784, RETOS-MINECO SAF2016-76565-R, ERANET-Neuron JTC 2019 ISCIII AC19/00077 FEDER funds (to R.A.); RETOS-MINECO SAF2017-87928-R (to A.B.); an NIH grant (NS76637) and UTHSC College of Medicine funds (to S.J.T.); and NARSAD Independent Investigator Award and grants from the MINECO (CSD2008-00005, SAF2013-48983R, SAF2016-80895-R), Generalitat Valenciana (PROMETEO 2019/020)(to I.P.O.) and Severo-Ochoa Excellence Awards (SEV-2013-0317, SEV-2017-0723).","author":[{"last_name":"Conde-Dusman","full_name":"Conde-Dusman, María J","first_name":"María J"},{"last_name":"Dey","full_name":"Dey, Partha N","first_name":"Partha N"},{"first_name":"Óscar","last_name":"Elía-Zudaire","full_name":"Elía-Zudaire, Óscar"},{"last_name":"Garcia Rabaneda","id":"33D1B084-F248-11E8-B48F-1D18A9856A87","full_name":"Garcia Rabaneda, Luis E","first_name":"Luis E"},{"first_name":"Carmen","last_name":"García-Lira","full_name":"García-Lira, Carmen"},{"full_name":"Grand, Teddy","last_name":"Grand","first_name":"Teddy"},{"full_name":"Briz, Victor","last_name":"Briz","first_name":"Victor"},{"full_name":"Velasco, Eric R","last_name":"Velasco","first_name":"Eric R"},{"last_name":"Andero Galí","full_name":"Andero Galí, Raül","first_name":"Raül"},{"first_name":"Sergio","last_name":"Niñerola","full_name":"Niñerola, Sergio"},{"first_name":"Angel","full_name":"Barco, Angel","last_name":"Barco"},{"first_name":"Pierre","last_name":"Paoletti","full_name":"Paoletti, Pierre"},{"first_name":"John F","full_name":"Wesseling, John F","last_name":"Wesseling"},{"full_name":"Gardoni, Fabrizio","last_name":"Gardoni","first_name":"Fabrizio"},{"first_name":"Steven J","full_name":"Tavalin, Steven J","last_name":"Tavalin"},{"last_name":"Perez-Otaño","full_name":"Perez-Otaño, Isabel","first_name":"Isabel"}],"type":"journal_article","status":"public","keyword":["general immunology and microbiology","general biochemistry","genetics and molecular biology","general medicine","general neuroscience"],"date_created":"2021-11-18T06:59:45Z","scopus_import":"1","publication":"eLife","language":[{"iso":"eng"}],"has_accepted_license":"1","ddc":["570"],"file":[{"content_type":"application/pdf","date_updated":"2021-11-18T07:02:02Z","file_name":"elife-71575-v1.pdf","creator":"lgarciar","file_id":"10302","checksum":"59318e9e41507cec83c2f4070e6ad540","date_created":"2021-11-18T07:02:02Z","file_size":2477302,"relation":"main_file","success":1,"access_level":"open_access"}],"intvolume":"        10"},{"title":"The logic of developing neocortical circuits in health and disease","isi":1,"month":"02","department":[{"_id":"SiHi"}],"date_updated":"2025-04-15T08:23:06Z","publication_status":"published","doi":"10.1523/jneurosci.1655-20.2020","article_processing_charge":"No","publication_identifier":{"issn":["0270-6474"],"eissn":["1529-2401"]},"publisher":"Society for Neuroscience","citation":{"apa":"Hanganu-Opatz, I. L., Butt, S. J. B., Hippenmeyer, S., De Marco García, N. V., Cardin, J. A., Voytek, B., &#38; Muotri, A. R. (2021). The logic of developing neocortical circuits in health and disease. <i>The Journal of Neuroscience</i>. Society for Neuroscience. <a href=\"https://doi.org/10.1523/jneurosci.1655-20.2020\">https://doi.org/10.1523/jneurosci.1655-20.2020</a>","short":"I.L. Hanganu-Opatz, S.J.B. Butt, S. Hippenmeyer, N.V. De Marco García, J.A. Cardin, B. Voytek, A.R. Muotri, The Journal of Neuroscience 41 (2021) 813–822.","chicago":"Hanganu-Opatz, Ileana L., Simon J. B. Butt, Simon Hippenmeyer, Natalia V. De Marco García, Jessica A. Cardin, Bradley Voytek, and Alysson R. Muotri. “The Logic of Developing Neocortical Circuits in Health and Disease.” <i>The Journal of Neuroscience</i>. Society for Neuroscience, 2021. <a href=\"https://doi.org/10.1523/jneurosci.1655-20.2020\">https://doi.org/10.1523/jneurosci.1655-20.2020</a>.","ama":"Hanganu-Opatz IL, Butt SJB, Hippenmeyer S, et al. The logic of developing neocortical circuits in health and disease. <i>The Journal of Neuroscience</i>. 2021;41(5):813-822. doi:<a href=\"https://doi.org/10.1523/jneurosci.1655-20.2020\">10.1523/jneurosci.1655-20.2020</a>","ista":"Hanganu-Opatz IL, Butt SJB, Hippenmeyer S, De Marco García NV, Cardin JA, Voytek B, Muotri AR. 2021. The logic of developing neocortical circuits in health and disease. The Journal of Neuroscience. 41(5), 813–822.","mla":"Hanganu-Opatz, Ileana L., et al. “The Logic of Developing Neocortical Circuits in Health and Disease.” <i>The Journal of Neuroscience</i>, vol. 41, no. 5, Society for Neuroscience, 2021, pp. 813–22, doi:<a href=\"https://doi.org/10.1523/jneurosci.1655-20.2020\">10.1523/jneurosci.1655-20.2020</a>.","ieee":"I. L. Hanganu-Opatz <i>et al.</i>, “The logic of developing neocortical circuits in health and disease,” <i>The Journal of Neuroscience</i>, vol. 41, no. 5. Society for Neuroscience, pp. 813–822, 2021."},"date_published":"2021-02-03T00:00:00Z","year":"2021","abstract":[{"lang":"eng","text":"The sensory and cognitive abilities of the mammalian neocortex are underpinned by intricate columnar and laminar circuits formed from an array of diverse neuronal populations. One approach to determining how interactions between these circuit components give rise to complex behavior is to investigate the rules by which cortical circuits are formed and acquire functionality during development. This review summarizes recent research on the development of the neocortex, from genetic determination in neural stem cells through to the dynamic role that specific neuronal populations play in the earliest circuits of neocortex, and how they contribute to emergent function and cognition. While many of these endeavors take advantage of model systems, consideration will also be given to advances in our understanding of activity in nascent human circuits. Such cross-species perspective is imperative when investigating the mechanisms underlying the dysfunction of early neocortical circuits in neurodevelopmental disorders, so that one can identify targets amenable to therapeutic intervention."}],"article_type":"original","project":[{"grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425"},{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F7805"}],"quality_controlled":"1","external_id":{"isi":["000616763400002"],"pmid":["33431633"]},"oa_version":"Published Version","day":"03","volume":41,"ec_funded":1,"type":"journal_article","author":[{"last_name":"Hanganu-Opatz","full_name":"Hanganu-Opatz, Ileana L.","first_name":"Ileana L."},{"first_name":"Simon J. B.","last_name":"Butt","full_name":"Butt, Simon J. B."},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","first_name":"Simon"},{"first_name":"Natalia V.","full_name":"De Marco García, Natalia V.","last_name":"De Marco García"},{"full_name":"Cardin, Jessica A.","last_name":"Cardin","first_name":"Jessica A."},{"first_name":"Bradley","last_name":"Voytek","full_name":"Voytek, Bradley"},{"last_name":"Muotri","full_name":"Muotri, Alysson R.","first_name":"Alysson R."}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","acknowledgement":"Work in the I.L.H.-O. laboratory was supported by European Research Council Grant ERC-2015-CoG 681577 and German Research Foundation Ha 4466/10-1, Ha4466/11-1, Ha4466/12-1, SPP 1665, and SFB 936B5. Work in the S.J.B.B. laboratory was supported by Biotechnology and Biological Sciences Research Council BB/P003796/1, Medical Research Council MR/K004387/1 and MR/T033320/1, Wellcome Trust 215199/Z/19/Z and 102386/Z/13/Z, and John Fell Fund. Work in the S.H. laboratory was supported by European Research Council Grants ERC-2016-CoG 725780 LinPro and FWF SFB F78. This work was supported by National Institutes of Health Grant NIMH 1R01MH110553 to N.V.D.M.G. Work in the J.A.C. laboratory was supported by the Ludwig Family Foundation, Simons Foundation SFARI Research Award, and National Institutes of Health/National Institute of Mental Health R01 MH102365 and R01MH113852. The B.V. laboratory was supported by Whitehall Foundation 2017-12-73, National Science Foundation 1736028, National Institutes of Health, National Institute of General Medical Sciences R01GM134363-01, and Halıcıoğlu Data Science Institute Fellowship. This work was supported by the University of California San Diego School of Medicine.","file_date_updated":"2022-05-27T06:59:55Z","issue":"5","_id":"9073","oa":1,"intvolume":"        41","page":"813-822","pmid":1,"file":[{"file_name":"2021_JourNeuroscience_Hanganu.pdf","date_updated":"2022-05-27T06:59:55Z","content_type":"application/pdf","creator":"dernst","file_id":"11414","date_created":"2022-05-27T06:59:55Z","checksum":"578fd7ed1a0aef74bce61bea2d987b33","access_level":"open_access","success":1,"relation":"main_file","file_size":1031150}],"ddc":["570"],"has_accepted_license":"1","language":[{"iso":"eng"}],"publication":"The Journal of Neuroscience","scopus_import":"1","date_created":"2021-02-03T12:23:51Z","keyword":["General Neuroscience"],"status":"public"},{"date_created":"2024-03-21T07:55:12Z","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"status":"public","scopus_import":"1","publication":"eLife","language":[{"iso":"eng"}],"intvolume":"         9","oa":1,"_id":"15153","extern":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"last_name":"Fribourgh","full_name":"Fribourgh, Jennifer L","first_name":"Jennifer L"},{"first_name":"Ashutosh","last_name":"Srivastava","full_name":"Srivastava, Ashutosh"},{"full_name":"Sandate, Colby R","last_name":"Sandate","first_name":"Colby R"},{"last_name":"Michael","full_name":"Michael, Alicia Kathleen","id":"6437c950-2a03-11ee-914d-d6476dd7b75c","first_name":"Alicia Kathleen"},{"last_name":"Hsu","full_name":"Hsu, Peter L","first_name":"Peter L"},{"first_name":"Christin","last_name":"Rakers","full_name":"Rakers, Christin"},{"first_name":"Leslee T","full_name":"Nguyen, Leslee T","last_name":"Nguyen"},{"first_name":"Megan R","last_name":"Torgrimson","full_name":"Torgrimson, Megan R"},{"full_name":"Parico, Gian Carlo G","last_name":"Parico","first_name":"Gian Carlo G"},{"last_name":"Tripathi","full_name":"Tripathi, Sarvind","first_name":"Sarvind"},{"first_name":"Ning","last_name":"Zheng","full_name":"Zheng, Ning"},{"first_name":"Gabriel C","last_name":"Lander","full_name":"Lander, Gabriel C"},{"first_name":"Tsuyoshi","full_name":"Hirota, Tsuyoshi","last_name":"Hirota"},{"first_name":"Florence","full_name":"Tama, Florence","last_name":"Tama"},{"first_name":"Carrie L","full_name":"Partch, Carrie L","last_name":"Partch"}],"type":"journal_article","day":"26","oa_version":"Published Version","volume":9,"quality_controlled":"1","main_file_link":[{"url":"https://doi.org/10.7554/eLife.55275","open_access":"1"}],"abstract":[{"text":"Mammalian circadian rhythms are generated by a transcription-based feedback loop in which CLOCK:BMAL1 drives transcription of its repressors (PER1/2, CRY1/2), which ultimately interact with CLOCK:BMAL1 to close the feedback loop with ~24 hr periodicity. Here we pinpoint a key difference between CRY1 and CRY2 that underlies their differential strengths as transcriptional repressors. Both cryptochromes bind the BMAL1 transactivation domain similarly to sequester it from coactivators and repress CLOCK:BMAL1 activity. However, we find that CRY1 is recruited with much higher affinity to the PAS domain core of CLOCK:BMAL1, allowing it to serve as a stronger repressor that lengthens circadian period. We discovered a dynamic serine-rich loop adjacent to the secondary pocket in the photolyase homology region (PHR) domain that regulates differential binding of cryptochromes to the PAS domain core of CLOCK:BMAL1. Notably, binding of the co-repressor PER2 remodels the serine loop of CRY2, making it more CRY1-like and enhancing its affinity for CLOCK:BMAL1.","lang":"eng"}],"article_type":"original","date_published":"2020-02-26T00:00:00Z","year":"2020","citation":{"apa":"Fribourgh, J. L., Srivastava, A., Sandate, C. R., Michael, A. K., Hsu, P. L., Rakers, C., … Partch, C. L. (2020). Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.55275\">https://doi.org/10.7554/elife.55275</a>","short":"J.L. Fribourgh, A. Srivastava, C.R. Sandate, A.K. Michael, P.L. Hsu, C. Rakers, L.T. Nguyen, M.R. Torgrimson, G.C.G. Parico, S. Tripathi, N. Zheng, G.C. Lander, T. Hirota, F. Tama, C.L. Partch, ELife 9 (2020).","chicago":"Fribourgh, Jennifer L, Ashutosh Srivastava, Colby R Sandate, Alicia K. Michael, Peter L Hsu, Christin Rakers, Leslee T Nguyen, et al. “Dynamics at the Serine Loop Underlie Differential Affinity of Cryptochromes for CLOCK:BMAL1 to Control Circadian Timing.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/elife.55275\">https://doi.org/10.7554/elife.55275</a>.","ama":"Fribourgh JL, Srivastava A, Sandate CR, et al. Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/elife.55275\">10.7554/elife.55275</a>","ista":"Fribourgh JL, Srivastava A, Sandate CR, Michael AK, Hsu PL, Rakers C, Nguyen LT, Torgrimson MR, Parico GCG, Tripathi S, Zheng N, Lander GC, Hirota T, Tama F, Partch CL. 2020. Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing. eLife. 9, 55275.","mla":"Fribourgh, Jennifer L., et al. “Dynamics at the Serine Loop Underlie Differential Affinity of Cryptochromes for CLOCK:BMAL1 to Control Circadian Timing.” <i>ELife</i>, vol. 9, 55275, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/elife.55275\">10.7554/elife.55275</a>.","ieee":"J. L. Fribourgh <i>et al.</i>, “Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020."},"publication_status":"published","article_processing_charge":"No","publisher":"eLife Sciences Publications","publication_identifier":{"issn":["2050-084X"]},"doi":"10.7554/elife.55275","date_updated":"2024-03-25T12:25:02Z","month":"02","title":"Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing","article_number":"55275"},{"date_published":"2020-06-17T00:00:00Z","year":"2020","citation":{"short":"U.H. Cho, M. Hetzer, Neuron 106 (2020) 899–911.","apa":"Cho, U. H., &#38; Hetzer, M. (2020). Nuclear periphery takes center stage: The role of nuclear pore complexes in cell identity and aging. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2020.05.031\">https://doi.org/10.1016/j.neuron.2020.05.031</a>","ama":"Cho UH, Hetzer M. Nuclear periphery takes center stage: The role of nuclear pore complexes in cell identity and aging. <i>Neuron</i>. 2020;106(6):899-911. doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.05.031\">10.1016/j.neuron.2020.05.031</a>","chicago":"Cho, Ukrae H., and Martin Hetzer. “Nuclear Periphery Takes Center Stage: The Role of Nuclear Pore Complexes in Cell Identity and Aging.” <i>Neuron</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.neuron.2020.05.031\">https://doi.org/10.1016/j.neuron.2020.05.031</a>.","ista":"Cho UH, Hetzer M. 2020. Nuclear periphery takes center stage: The role of nuclear pore complexes in cell identity and aging. Neuron. 106(6), 899–911.","ieee":"U. H. Cho and M. Hetzer, “Nuclear periphery takes center stage: The role of nuclear pore complexes in cell identity and aging,” <i>Neuron</i>, vol. 106, no. 6. Elsevier, pp. 899–911, 2020.","mla":"Cho, Ukrae H., and Martin Hetzer. “Nuclear Periphery Takes Center Stage: The Role of Nuclear Pore Complexes in Cell Identity and Aging.” <i>Neuron</i>, vol. 106, no. 6, Elsevier, 2020, pp. 899–911, doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.05.031\">10.1016/j.neuron.2020.05.031</a>."},"publication_identifier":{"issn":["0896-6273"]},"article_processing_charge":"No","publisher":"Elsevier","doi":"10.1016/j.neuron.2020.05.031","publication_status":"published","date_updated":"2024-10-14T11:15:26Z","month":"06","title":"Nuclear periphery takes center stage: The role of nuclear pore complexes in cell identity and aging","day":"17","oa_version":"Published Version","volume":106,"external_id":{"pmid":["32553207"]},"quality_controlled":"1","article_type":"review","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.neuron.2020.05.031"}],"abstract":[{"lang":"eng","text":"In recent years, the nuclear pore complex (NPC) has emerged as a key player in genome regulation and cellular homeostasis. New discoveries have revealed that the NPC has multiple cellular functions besides mediating the molecular exchange between the nucleus and the cytoplasm. In this review, we discuss non-transport aspects of the NPC focusing on the NPC-genome interaction, the extreme longevity of the NPC proteins, and NPC dysfunction in age-related diseases. The examples summarized herein demonstrate that the NPC, which first evolved to enable the biochemical communication between the nucleus and the cytoplasm, now doubles as the gatekeeper of cellular identity and aging."}],"oa":1,"_id":"11054","issue":"6","author":[{"first_name":"Ukrae H.","full_name":"Cho, Ukrae H.","last_name":"Cho"},{"orcid":"0000-0002-2111-992X","first_name":"Martin W","last_name":"HETZER","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","full_name":"HETZER, Martin W"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"journal_article","extern":"1","status":"public","scopus_import":"1","date_created":"2022-04-07T07:43:36Z","keyword":["General Neuroscience"],"publication":"Neuron","language":[{"iso":"eng"}],"pmid":1,"page":"899-911","intvolume":"       106"},{"pmid":1,"intvolume":"         9","file":[{"content_type":"application/pdf","date_updated":"2022-04-08T06:53:10Z","file_name":"2020_eLife_Bersini.pdf","file_id":"11132","creator":"dernst","checksum":"f8b3821349a194050be02570d8fe7d4b","date_created":"2022-04-08T06:53:10Z","file_size":4399825,"relation":"main_file","success":1,"access_level":"open_access"}],"ddc":["570"],"has_accepted_license":"1","publication":"eLife","language":[{"iso":"eng"}],"status":"public","date_created":"2022-04-07T07:43:48Z","scopus_import":"1","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"extern":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"first_name":"Simone","last_name":"Bersini","full_name":"Bersini, Simone"},{"first_name":"Roberta","last_name":"Schulte","full_name":"Schulte, Roberta"},{"first_name":"Ling","last_name":"Huang","full_name":"Huang, Ling"},{"full_name":"Tsai, Hannah","last_name":"Tsai","first_name":"Hannah"},{"last_name":"HETZER","full_name":"HETZER, Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","first_name":"Martin W","orcid":"0000-0002-2111-992X"}],"type":"journal_article","file_date_updated":"2022-04-08T06:53:10Z","_id":"11055","oa":1,"abstract":[{"text":"Vascular dysfunctions are a common feature of multiple age-related diseases. However, modeling healthy and pathological aging of the human vasculature represents an unresolved experimental challenge. Here, we generated induced vascular endothelial cells (iVECs) and smooth muscle cells (iSMCs) by direct reprogramming of healthy human fibroblasts from donors of different ages and Hutchinson-Gilford Progeria Syndrome (HGPS) patients. iVECs induced from old donors revealed upregulation of GSTM1 and PALD1, genes linked to oxidative stress, inflammation and endothelial junction stability, as vascular aging markers. A functional assay performed on PALD1 KD VECs demonstrated a recovery in vascular permeability. We found that iSMCs from HGPS donors overexpressed bone morphogenetic protein (BMP)−4, which plays a key role in both vascular calcification and endothelial barrier damage observed in HGPS. Strikingly, BMP4 concentrations are higher in serum from HGPS vs. age-matched mice. Furthermore, targeting BMP4 with blocking antibody recovered the functionality of the vascular barrier in vitro, hence representing a potential future therapeutic strategy to limit cardiovascular dysfunction in HGPS. These results show that iVECs and iSMCs retain disease-related signatures, allowing modeling of vascular aging and HGPS in vitro.","lang":"eng"}],"article_type":"original","external_id":{"pmid":["32896271"]},"quality_controlled":"1","oa_version":"Published Version","day":"08","volume":9,"title":"Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome","article_number":"e54383","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"date_updated":"2024-10-14T11:17:02Z","month":"09","publication_status":"published","article_processing_charge":"No","publisher":"eLife Sciences Publications","publication_identifier":{"issn":["2050-084X"]},"doi":"10.7554/elife.54383","date_published":"2020-09-08T00:00:00Z","year":"2020","citation":{"apa":"Bersini, S., Schulte, R., Huang, L., Tsai, H., &#38; Hetzer, M. (2020). Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.54383\">https://doi.org/10.7554/elife.54383</a>","short":"S. Bersini, R. Schulte, L. Huang, H. Tsai, M. Hetzer, ELife 9 (2020).","chicago":"Bersini, Simone, Roberta Schulte, Ling Huang, Hannah Tsai, and Martin Hetzer. “Direct Reprogramming of Human Smooth Muscle and Vascular Endothelial Cells Reveals Defects Associated with Aging and Hutchinson-Gilford Progeria Syndrome.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/elife.54383\">https://doi.org/10.7554/elife.54383</a>.","ama":"Bersini S, Schulte R, Huang L, Tsai H, Hetzer M. Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/elife.54383\">10.7554/elife.54383</a>","ista":"Bersini S, Schulte R, Huang L, Tsai H, Hetzer M. 2020. Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome. eLife. 9, e54383.","mla":"Bersini, Simone, et al. “Direct Reprogramming of Human Smooth Muscle and Vascular Endothelial Cells Reveals Defects Associated with Aging and Hutchinson-Gilford Progeria Syndrome.” <i>ELife</i>, vol. 9, e54383, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/elife.54383\">10.7554/elife.54383</a>.","ieee":"S. Bersini, R. Schulte, L. Huang, H. Tsai, and M. Hetzer, “Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020."}}]