[{"OA_place":"publisher","corr_author":"1","PlanS_conform":"1","license":"https://creativecommons.org/licenses/by/4.0/","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"language":[{"iso":"eng"}],"oa":1,"has_accepted_license":"1","article_processing_charge":"Yes","file_date_updated":"2025-12-30T09:17:09Z","isi":1,"fulldoi":"https://doi.org/10.26508/lsa.202503208","title":"PSME3 regulates migration and differentiation of myoblasts","file":[{"date_created":"2025-12-30T09:17:09Z","content_type":"application/pdf","access_level":"open_access","file_name":"2025_LifeScienceAlliance_Kuhn.pdf","date_updated":"2025-12-30T09:17:09Z","success":1,"relation":"main_file","creator":"dernst","checksum":"591d47aa39fc969986c7d3b966890f5f","file_size":5471288,"file_id":"20904"}],"project":[{"_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854","name":"IST Austria Open Access Fund"}],"publication_status":"published","ddc":["570"],"OA_type":"gold","APC_amount":"4215,38 EUR","type":"journal_article","status":"public","intvolume":"         8","volume":8,"publication_identifier":{"eissn":["2575-1077"]},"article_type":"original","quality_controlled":"1","article_number":"e202503208","issue":"9","pmid":1,"acknowledgement":"All proteomics analysis was done by the ISTA LSF Mass Spectrometry Service: Ewelina Dutkiewicz-Kopczynska processed the samples (digest and cleanup); Bella Bruszel optimized the acquisition methods, acquired the data, and performed all searches; and Armel Nicolas provided pre- and post-project consulting and post-processed the search results using a development version of their data analysis package, proteoCraft (publication pending). The authors would like to thank Saki for their clarity of thought and insight, as well as Dr. Lorenzo Puri and the members of his laboratory for invaluable discussions relating to the project. This research was further supported by the Lab Support Facility and the Imaging and Optics Facility of ISTA.","_id":"19963","department":[{"_id":"MaHe"}],"month":"09","oa_version":"Published Version","publisher":"Embo Press","external_id":{"pmid":["40537284"],"isi":["001511452100001"]},"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"abstract":[{"text":"The acquisition of cellular identity requires large-scale alterations in cellular state. The noncanonical proteasome activator PSME3 is known to regulate diverse cellular processes, but its importance for differentiation remains unclear. Here, we demonstrate that PSME3 binds dynamically to highly active promoters over the course of differentiation. However, loss of PSME3 does not globally affect mRNA transcription. We find instead that PSME3 influences the levels of several adhesion-related proteins and acts upstream of the HSP90 co-chaperone NUDC to regulate cell motility and myoblast differentiation in a proteasome-independent manner. Our findings reveal several new facets of PSME3 functionality and highlight its importance for the differentiation of myogenic cells.","lang":"eng"}],"scopus_import":"1","doi":"10.26508/lsa.202503208","date_published":"2025-09-01T00:00:00Z","DOAJ_listed":"1","day":"01","year":"2025","date_created":"2025-07-06T22:01:22Z","citation":{"chicago":"Kuhn, Kenneth D, Ukrae H. Cho, and Martin Hetzer. “PSME3 Regulates Migration and Differentiation of Myoblasts.” <i>Life Science Alliance</i>. Embo Press, 2025. <a href=\"https://doi.org/10.26508/lsa.202503208\">https://doi.org/10.26508/lsa.202503208</a>.","ieee":"K. D. Kuhn, U. H. Cho, and M. Hetzer, “PSME3 regulates migration and differentiation of myoblasts,” <i>Life Science Alliance</i>, vol. 8, no. 9. Embo Press, 2025.","short":"K.D. Kuhn, U.H. Cho, M. Hetzer, Life Science Alliance 8 (2025).","mla":"Kuhn, Kenneth D., et al. “PSME3 Regulates Migration and Differentiation of Myoblasts.” <i>Life Science Alliance</i>, vol. 8, no. 9, e202503208, Embo Press, 2025, doi:<a href=\"https://doi.org/10.26508/lsa.202503208\">10.26508/lsa.202503208</a>.","ama":"Kuhn KD, Cho UH, Hetzer M. PSME3 regulates migration and differentiation of myoblasts. <i>Life Science Alliance</i>. 2025;8(9). doi:<a href=\"https://doi.org/10.26508/lsa.202503208\">10.26508/lsa.202503208</a>","ista":"Kuhn KD, Cho UH, Hetzer M. 2025. PSME3 regulates migration and differentiation of myoblasts. Life Science Alliance. 8(9), e202503208.","apa":"Kuhn, K. D., Cho, U. H., &#38; Hetzer, M. (2025). PSME3 regulates migration and differentiation of myoblasts. <i>Life Science Alliance</i>. Embo Press. <a href=\"https://doi.org/10.26508/lsa.202503208\">https://doi.org/10.26508/lsa.202503208</a>"},"publication":"Life Science Alliance","author":[{"full_name":"Kuhn, Kenneth D","last_name":"Kuhn","first_name":"Kenneth D","id":"7deed7e0-0133-11f0-8590-c4600b08d0f4"},{"first_name":"Ukrae H.","last_name":"Cho","full_name":"Cho, Ukrae H."},{"full_name":"Hetzer, Martin W","orcid":"0000-0002-2111-992X","first_name":"Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","last_name":"Hetzer"}],"date_updated":"2026-05-20T08:38:04Z"},{"external_id":{"pmid":["40744775"],"isi":["001568965400001"]},"publisher":"Cell Press","month":"09","oa_version":"Published Version","department":[{"_id":"MaHe"}],"_id":"20154","acknowledgement":"The work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) (470322152 – T1347/3-1; 497658532 – T1347/4-1; 507965872 – T1347/5-1; and 460333672 – CRC1540 Exploring Brain Mechanics) to T.T., the Schram Foundation (T.T.), the European Research Council (ERC-2018-STG, 804468 EAGER; ERC-2023-COG, 101125034 NEUTIME) to T.T., the Hans-Georg Geis und Xue Hong Dong-Geis Foundation and Forschungsstiftung Medizin am Universitätsklinikum Erlangen to T.T., and the Interdisciplinary Centre for Clinical Research Erlangen (Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Erlangen; P162 to T.T.). We thank Dr Laura J. Harrison for editing assistance.","pmid":1,"issue":"9","quality_controlled":"1","publication_identifier":{"issn":["0166-2236"],"eissn":["1878-108X"]},"article_type":"original","volume":48,"intvolume":"        48","date_updated":"2026-10-20T08:54:50Z","author":[{"full_name":"Hetzer, Martin W","orcid":"0000-0002-2111-992X","first_name":"Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","last_name":"Hetzer"},{"full_name":"Toda, Tomohisa","first_name":"Tomohisa","last_name":"Toda"}],"publication":"Trends in Neurosciences","citation":{"chicago":"Hetzer, Martin, and Tomohisa Toda. “Long-Lived Cellular Molecules in the Brain.” <i>Trends in Neurosciences</i>. Cell Press, 2025. <a href=\"https://doi.org/10.1016/j.tins.2025.07.004\">https://doi.org/10.1016/j.tins.2025.07.004</a>.","mla":"Hetzer, Martin, and Tomohisa Toda. “Long-Lived Cellular Molecules in the Brain.” <i>Trends in Neurosciences</i>, vol. 48, no. 9, Cell Press, 2025, pp. 645–54, doi:<a href=\"https://doi.org/10.1016/j.tins.2025.07.004\">10.1016/j.tins.2025.07.004</a>.","ieee":"M. Hetzer and T. Toda, “Long-lived cellular molecules in the brain,” <i>Trends in Neurosciences</i>, vol. 48, no. 9. Cell Press, pp. 645–654, 2025.","short":"M. Hetzer, T. Toda, Trends in Neurosciences 48 (2025) 645–654.","ista":"Hetzer M, Toda T. 2025. Long-lived cellular molecules in the brain. Trends in Neurosciences. 48(9), 645–654.","ama":"Hetzer M, Toda T. Long-lived cellular molecules in the brain. <i>Trends in Neurosciences</i>. 2025;48(9):645-654. doi:<a href=\"https://doi.org/10.1016/j.tins.2025.07.004\">10.1016/j.tins.2025.07.004</a>","apa":"Hetzer, M., &#38; Toda, T. (2025). Long-lived cellular molecules in the brain. <i>Trends in Neurosciences</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.tins.2025.07.004\">https://doi.org/10.1016/j.tins.2025.07.004</a>"},"date_created":"2025-08-10T22:01:29Z","year":"2025","day":"01","date_published":"2025-09-01T00:00:00Z","doi":"10.1016/j.tins.2025.07.004","scopus_import":"1","abstract":[{"text":"In long-lived mammals, including humans, brain cell homeostasis is critical for maintaining brain function throughout life. Most neurons are generated during development and must maintain their cellular identity and plasticity to preserve brain function. Although extensive studies indicate the importance of recycling and regenerating cellular molecules to maintain cellular homeostasis, recent evidence has shown that some proteins and RNAs do not turn over for months and even years. We propose that these long-lived cellular molecules may be the basis for maintaining brain function in the long term, but also a potential convergent target of brain aging. We highlight key discoveries and challenges, and propose potential directions to unravel the mystery of brain cell longevity.","lang":"eng"}],"file_date_updated":"2025-12-29T13:47:27Z","article_processing_charge":"Yes (in subscription journal)","has_accepted_license":"1","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"language":[{"iso":"eng"}],"page":"645-654","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","PlanS_conform":"1","corr_author":"1","OA_place":"publisher","status":"public","type":"journal_article","OA_type":"hybrid","ddc":["570"],"publication_status":"published","title":"Long-lived cellular molecules in the brain","file":[{"creator":"dernst","checksum":"90942491b499f70b0bf48b8aec2e7387","file_id":"20873","file_size":327847,"date_created":"2025-12-29T13:47:27Z","content_type":"application/pdf","file_name":"2025_TrendsNeurosciences_Hetzer.pdf","access_level":"open_access","relation":"main_file","success":1,"date_updated":"2025-12-29T13:47:27Z"}],"fulldoi":"https://doi.org/10.1016/j.tins.2025.07.004","isi":1},{"das_tickbox":"1","abstract":[{"lang":"eng","text":"Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging metabolomics demonstrates that beta cells upon CR are more energetically competent. In fact, high-resolution microscopy show that CR reduces beta cell mitophagy to increase mitochondria mass and the potential for ATP generation. However, CR beta cells have impaired adaptive proliferation in response to high fat diet feeding. Finally, we show that long-term CR delays the onset of beta cell aging hallmarks and promotes cell longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cell structure-function during aging and diabetes."}],"scopus_import":"1","doi":"10.1038/s41467-024-53127-2","DOAJ_listed":"1","date_published":"2024-10-21T00:00:00Z","day":"21","year":"2024","date_created":"2024-10-27T23:01:44Z","citation":{"mla":"Dos Santos, Cristiane, et al. “Calorie Restriction Increases Insulin Sensitivity to Promote Beta Cell Homeostasis and Longevity in Mice.” <i>Nature Communications</i>, vol. 15, 9063, Springer Nature, 2024, doi:<a href=\"https://doi.org/10.1038/s41467-024-53127-2\">10.1038/s41467-024-53127-2</a>.","short":"C. Dos Santos, A. Cambraia, S. Shrestha, M. Cutler, M. Cottam, G. Perkins, V. Lev-Ram, B. Roy, C. Acree, K.Y. Kim, T. Deerinck, D. Dean, J.P. Cartailler, P.E. Macdonald, M. Hetzer, M. Ellisman, R. Arrojo E Drigo, Nature Communications 15 (2024).","ieee":"C. Dos Santos <i>et al.</i>, “Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice,” <i>Nature Communications</i>, vol. 15. Springer Nature, 2024.","chicago":"Dos Santos, Cristiane, Amanda Cambraia, Shristi Shrestha, Melanie Cutler, Matthew Cottam, Guy Perkins, Varda Lev-Ram, et al. “Calorie Restriction Increases Insulin Sensitivity to Promote Beta Cell Homeostasis and Longevity in Mice.” <i>Nature Communications</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41467-024-53127-2\">https://doi.org/10.1038/s41467-024-53127-2</a>.","apa":"Dos Santos, C., Cambraia, A., Shrestha, S., Cutler, M., Cottam, M., Perkins, G., … Arrojo E Drigo, R. (2024). Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-024-53127-2\">https://doi.org/10.1038/s41467-024-53127-2</a>","ama":"Dos Santos C, Cambraia A, Shrestha S, et al. Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice. <i>Nature Communications</i>. 2024;15. doi:<a href=\"https://doi.org/10.1038/s41467-024-53127-2\">10.1038/s41467-024-53127-2</a>","ista":"Dos Santos C, Cambraia A, Shrestha S, Cutler M, Cottam M, Perkins G, Lev-Ram V, Roy B, Acree C, Kim KY, Deerinck T, Dean D, Cartailler JP, Macdonald PE, Hetzer M, Ellisman M, Arrojo E Drigo R. 2024. Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice. Nature Communications. 15, 9063."},"publication":"Nature Communications","author":[{"full_name":"Dos Santos, Cristiane","last_name":"Dos Santos","first_name":"Cristiane"},{"first_name":"Amanda","last_name":"Cambraia","full_name":"Cambraia, Amanda"},{"full_name":"Shrestha, Shristi","last_name":"Shrestha","first_name":"Shristi"},{"last_name":"Cutler","first_name":"Melanie","full_name":"Cutler, Melanie"},{"first_name":"Matthew","last_name":"Cottam","full_name":"Cottam, Matthew"},{"last_name":"Perkins","first_name":"Guy","full_name":"Perkins, Guy"},{"first_name":"Varda","last_name":"Lev-Ram","full_name":"Lev-Ram, Varda"},{"full_name":"Roy, Birbickram","last_name":"Roy","first_name":"Birbickram"},{"last_name":"Acree","first_name":"Christopher","full_name":"Acree, Christopher"},{"last_name":"Kim","first_name":"Keun Young","full_name":"Kim, Keun Young"},{"full_name":"Deerinck, Thomas","first_name":"Thomas","last_name":"Deerinck"},{"last_name":"Dean","first_name":"Danielle","full_name":"Dean, Danielle"},{"last_name":"Cartailler","first_name":"Jean Philippe","full_name":"Cartailler, Jean Philippe"},{"full_name":"Macdonald, Patrick E.","first_name":"Patrick E.","last_name":"Macdonald"},{"full_name":"Hetzer, Martin W","orcid":"0000-0002-2111-992X","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","first_name":"Martin W","last_name":"Hetzer"},{"full_name":"Ellisman, Mark","first_name":"Mark","last_name":"Ellisman"},{"first_name":"Rafael","last_name":"Arrojo E Drigo","full_name":"Arrojo E Drigo, Rafael"}],"date_updated":"2026-10-16T09:00:16Z","intvolume":"        15","volume":15,"researchdata_availability":"yes","publication_identifier":{"eissn":["2041-1723"]},"article_type":"original","quality_controlled":"1","article_number":"9063","pmid":1,"acknowledgement":"We are thankful to Michelle Reyzer from the Vanderbilt Mass Spectrometry Research Center for assistance with MALDI-MS imaging and analysis, to the outstanding team at the Vanderbilt Mouse Metabolic Phenotyping Center for all the assistance with in vivo glucose homeostasis tests (DK135073, 1S10RR028101-01). We also thank the University of Michigan Animal Phenotyping Core for conducting the bomb calorimetry experiments (1U2CDK110768, DK020575, and DK089503). This research was supported by recruitment funds from the Vanderbilt’s Department of Molecular Physiology and Biophysics and NIH grants 1R03DK127484, 5U24DK097771, and 1R01DK138141 to RAeD, by a grant from the Canadian Institutes of Health Research (CIHR; 487188) to PEM, by and NIH DK132669 to D.D. PEM holds the Canada Research Chair in Islet Biology.","_id":"18480","department":[{"_id":"MaHe"}],"month":"10","oa_version":"Published Version","publisher":"Springer Nature","external_id":{"isi":["001426270600023"],"pmid":["39433757"]},"isi":1,"fulldoi":"https://doi.org/10.1038/s41467-024-53127-2","file":[{"file_id":"18502","file_size":7358742,"checksum":"b936b1c047f41cd427f00e3dc79327d3","creator":"dernst","success":1,"date_updated":"2024-11-04T10:37:56Z","relation":"main_file","file_name":"2024_NatureComm_dosSantos.pdf","access_level":"open_access","date_created":"2024-11-04T10:37:56Z","content_type":"application/pdf"}],"title":"Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice","publication_status":"published","ddc":["570"],"OA_type":"gold","type":"journal_article","status":"public","OA_place":"publisher","supplementarymaterial":"yes","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"dataavailabilitystatement":"Tabular and processed sequencing data is deposited in Zenodo (https://doi.org/10.5281/zenodo.6491943). The single nucleus multiome sequencing data has been deposited in the GEO repository (GSE276572, https://www.ncbi.xyz/geo/query/acc.cgi?acc=GSE276572). Source data are provided with this paper.","oa":1,"related_material":{"record":[{"relation":"research_data","id":"22865","status":"public"}]},"has_accepted_license":"1","file_date_updated":"2024-11-04T10:37:56Z","article_processing_charge":"Yes"},{"fulldoi":"https://doi.org/10.1126/science.adf3481","isi":1,"title":"Lifelong persistence of nuclear RNAs in the mouse brain","publication_status":"published","OA_type":"green","type":"journal_article","status":"public","OA_place":"repository","corr_author":"1","supplementarymaterial":"yes","dataavailabilitystatement":"All data are available in the main text, figures, or supplementary materials. EU-RNA-seq data were submitted to the Gene Expression Omnibus (GEO) under accession no. GSE248101.","page":"53-59","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","language":[{"iso":"eng"}],"article_processing_charge":"No","oa":1,"related_material":{"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/nerve-cells-old-at-heart/","description":"News on ISTA website"}]},"das_tickbox":"1","doi":"10.1126/science.adf3481","date_published":"2024-04-04T00:00:00Z","day":"04","abstract":[{"lang":"eng","text":"Genomic DNA that resides in the nuclei of mammalian neurons can be as old as the organism itself. The life span of nuclear RNAs, which are critical for proper chromatin architecture and transcription regulation, has not been determined in adult tissues. In this work, we identified and characterized nuclear RNAs that do not turn over for at least 2 years in a subset of postnatally born cells in the mouse brain. These long-lived RNAs were stably retained in nuclei in a neural cell type–specific manner and were required for the maintenance of heterochromatin. Thus, the life span of neural cells may depend on both the molecular longevity of DNA for the storage of genetic information and also the extreme stability of RNA for the functional organization of chromatin."}],"scopus_import":"1","publication":"Science","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615865","open_access":"1"}],"year":"2024","date_created":"2024-04-14T22:01:01Z","citation":{"mla":"Zocher, Sara, et al. “Lifelong Persistence of Nuclear RNAs in the Mouse Brain.” <i>Science</i>, vol. 384, no. 6691, AAAS, 2024, pp. 53–59, doi:<a href=\"https://doi.org/10.1126/science.adf3481\">10.1126/science.adf3481</a>.","ieee":"S. Zocher <i>et al.</i>, “Lifelong persistence of nuclear RNAs in the mouse brain,” <i>Science</i>, vol. 384, no. 6691. AAAS, pp. 53–59, 2024.","short":"S. Zocher, A. Mccloskey, A. Karasinsky, R. Schulte, U. Friedrich, M. Lesche, N. Rund, F.H. Gage, M. Hetzer, T. Toda, Science 384 (2024) 53–59.","chicago":"Zocher, Sara, Asako Mccloskey, Anne Karasinsky, Roberta Schulte, Ulrike Friedrich, Mathias Lesche, Nicole Rund, Fred H. Gage, Martin Hetzer, and Tomohisa Toda. “Lifelong Persistence of Nuclear RNAs in the Mouse Brain.” <i>Science</i>. AAAS, 2024. <a href=\"https://doi.org/10.1126/science.adf3481\">https://doi.org/10.1126/science.adf3481</a>.","apa":"Zocher, S., Mccloskey, A., Karasinsky, A., Schulte, R., Friedrich, U., Lesche, M., … Toda, T. (2024). Lifelong persistence of nuclear RNAs in the mouse brain. <i>Science</i>. AAAS. <a href=\"https://doi.org/10.1126/science.adf3481\">https://doi.org/10.1126/science.adf3481</a>","ama":"Zocher S, Mccloskey A, Karasinsky A, et al. Lifelong persistence of nuclear RNAs in the mouse brain. <i>Science</i>. 2024;384(6691):53-59. doi:<a href=\"https://doi.org/10.1126/science.adf3481\">10.1126/science.adf3481</a>","ista":"Zocher S, Mccloskey A, Karasinsky A, Schulte R, Friedrich U, Lesche M, Rund N, Gage FH, Hetzer M, Toda T. 2024. Lifelong persistence of nuclear RNAs in the mouse brain. Science. 384(6691), 53–59."},"date_updated":"2026-10-16T08:59:32Z","author":[{"full_name":"Zocher, Sara","first_name":"Sara","last_name":"Zocher"},{"last_name":"Mccloskey","first_name":"Asako","full_name":"Mccloskey, Asako"},{"last_name":"Karasinsky","first_name":"Anne","full_name":"Karasinsky, Anne"},{"full_name":"Schulte, Roberta","first_name":"Roberta","last_name":"Schulte"},{"last_name":"Friedrich","first_name":"Ulrike","full_name":"Friedrich, Ulrike"},{"last_name":"Lesche","first_name":"Mathias","full_name":"Lesche, Mathias"},{"full_name":"Rund, Nicole","first_name":"Nicole","last_name":"Rund"},{"last_name":"Gage","first_name":"Fred H.","full_name":"Gage, Fred H."},{"last_name":"Hetzer","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","first_name":"Martin W","orcid":"0000-0002-2111-992X","full_name":"Hetzer, Martin W"},{"full_name":"Toda, Tomohisa","last_name":"Toda","first_name":"Tomohisa"}],"researchdata_availability":"yes","volume":384,"article_type":"original","publication_identifier":{"issn":["0036-8075"],"eissn":["1095-9203"]},"intvolume":"       384","pmid":1,"issue":"6691","quality_controlled":"1","_id":"15316","department":[{"_id":"MaHe"}],"acknowledgement":"European Research Council: ERC-2018-STG, 804468 EAGER; European Research Council: ERC-2023-COG, 101125034 NEUTIME; Deutsche Forschungsgemeinschaft: TO1347/4-1; Boehringer Ingelheim Stiftung; Deutsches Zentrum für Neurodegenerative Erkrankungen","external_id":{"isi":["001253335100031"],"pmid":["38574132"]},"month":"04","oa_version":"Submitted Version","publisher":"AAAS"},{"isi":1,"fulldoi":"https://doi.org/10.1080/19491034.2023.2202548","publication_status":"published","file":[{"date_created":"2023-05-02T07:24:55Z","content_type":"application/pdf","file_name":"2023_Nucleus_Kaneshiro.pdf","access_level":"open_access","success":1,"date_updated":"2023-05-02T07:24:55Z","relation":"main_file","creator":"dernst","checksum":"8e707eda84f64dbad7f03545ae0a83ef","file_size":3811113,"file_id":"12884"}],"title":"Lamin B1 overexpression alters chromatin organization and gene expression","ddc":["570"],"type":"journal_article","status":"public","corr_author":"1","license":"https://creativecommons.org/licenses/by-nc/4.0/","tmp":{"short":"CC BY-NC (4.0)","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","image":"/images/cc_by_nc.png","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode"},"language":[{"iso":"eng"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"has_accepted_license":"1","file_date_updated":"2023-05-02T07:24:55Z","article_processing_charge":"No","abstract":[{"text":"Peripheral heterochromatin positioning depends on nuclear envelope associated proteins and repressive histone modifications. Here we show that overexpression (OE) of Lamin B1 (LmnB1) leads to the redistribution of peripheral heterochromatin into heterochromatic foci within the nucleoplasm. These changes represent a perturbation of heterochromatin binding at the nuclear periphery (NP) through a mechanism independent from altering other heterochromatin anchors or histone post-translational modifications. We further show that LmnB1 OE alters gene expression. These changes do not correlate with different levels of H3K9me3, but a significant number of the misregulated genes were likely mislocalized away from the NP upon LmnB1 OE. We also observed an enrichment of developmental processes amongst the upregulated genes. ~74% of these genes were normally repressed in our cell type, suggesting that LmnB1 OE promotes gene de-repression. This demonstrates a broader consequence of LmnB1 OE on cell fate, and highlights the importance of maintaining proper levels of LmnB1.","lang":"eng"}],"scopus_import":"1","date_published":"2023-04-18T00:00:00Z","day":"18","doi":"10.1080/19491034.2023.2202548","citation":{"chicago":"Kaneshiro, Jeanae M., Juliana S. Capitanio, and Martin Hetzer. “Lamin B1 Overexpression Alters Chromatin Organization and Gene Expression.” <i>Nucleus</i>. Taylor &#38; Francis, 2023. <a href=\"https://doi.org/10.1080/19491034.2023.2202548\">https://doi.org/10.1080/19491034.2023.2202548</a>.","short":"J.M. Kaneshiro, J.S. Capitanio, M. Hetzer, Nucleus 14 (2023).","ieee":"J. M. Kaneshiro, J. S. Capitanio, and M. Hetzer, “Lamin B1 overexpression alters chromatin organization and gene expression,” <i>Nucleus</i>, vol. 14, no. 1. Taylor &#38; Francis, 2023.","mla":"Kaneshiro, Jeanae M., et al. “Lamin B1 Overexpression Alters Chromatin Organization and Gene Expression.” <i>Nucleus</i>, vol. 14, no. 1, 2202548, Taylor &#38; Francis, 2023, doi:<a href=\"https://doi.org/10.1080/19491034.2023.2202548\">10.1080/19491034.2023.2202548</a>.","ista":"Kaneshiro JM, Capitanio JS, Hetzer M. 2023. Lamin B1 overexpression alters chromatin organization and gene expression. Nucleus. 14(1), 2202548.","ama":"Kaneshiro JM, Capitanio JS, Hetzer M. Lamin B1 overexpression alters chromatin organization and gene expression. <i>Nucleus</i>. 2023;14(1). doi:<a href=\"https://doi.org/10.1080/19491034.2023.2202548\">10.1080/19491034.2023.2202548</a>","apa":"Kaneshiro, J. M., Capitanio, J. S., &#38; Hetzer, M. (2023). Lamin B1 overexpression alters chromatin organization and gene expression. <i>Nucleus</i>. Taylor &#38; Francis. <a href=\"https://doi.org/10.1080/19491034.2023.2202548\">https://doi.org/10.1080/19491034.2023.2202548</a>"},"date_created":"2023-04-30T22:01:06Z","year":"2023","publication":"Nucleus","author":[{"last_name":"Kaneshiro","first_name":"Jeanae M.","full_name":"Kaneshiro, Jeanae M."},{"last_name":"Capitanio","first_name":"Juliana S.","full_name":"Capitanio, Juliana S."},{"last_name":"Hetzer","first_name":"Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","orcid":"0000-0002-2111-992X","full_name":"Hetzer, Martin W"}],"date_updated":"2024-10-09T21:05:01Z","intvolume":"        14","publication_identifier":{"eissn":["1949-1042"],"issn":["1949-1034"]},"article_type":"original","volume":14,"quality_controlled":"1","issue":"1","pmid":1,"article_number":"2202548","acknowledgement":"We thank members of the Hetzer lab for critical review of the manuscript; Novogene for mRNA library preparation and sequencing; the Next-Generation Sequencing Core Facility at the Salk Institute, with funding from NIH-NCI CCSG: P30 014195, the Chapman Foundation, and the Helmsley Charitable Trust, for sequencing Cut&Run libraries; and the Waitt Advanced Biophotonics Core Facility at the Salk Institute, with funding from NIH-NCI CCSG: P30 014195, the Waitt Foundation, and the Chan-Zuckerberg Initiative Imaging Scientist Award, for electron microscopy sample preparation and imaging.","department":[{"_id":"MaHe"}],"_id":"12880","publisher":"Taylor & Francis","month":"04","oa_version":"Published Version","external_id":{"isi":["000971629400001"],"pmid":["37071033"]}},{"author":[{"full_name":"Cho, Ukrae H.","last_name":"Cho","first_name":"Ukrae H."},{"last_name":"Hetzer","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","first_name":"Martin W","orcid":"0000-0002-2111-992X","full_name":"Hetzer, Martin W"}],"date_updated":"2024-10-09T21:06:57Z","year":"2023","date_created":"2023-09-10T22:01:11Z","citation":{"chicago":"Cho, Ukrae H., and Martin Hetzer. “Caspase-Mediated Nuclear Pore Complex Trimming in Cell Differentiation and Endoplasmic Reticulum Stress.” <i>ELife</i>. eLife Sciences Publications, 2023. <a href=\"https://doi.org/10.7554/eLife.89066\">https://doi.org/10.7554/eLife.89066</a>.","mla":"Cho, Ukrae H., and Martin Hetzer. “Caspase-Mediated Nuclear Pore Complex Trimming in Cell Differentiation and Endoplasmic Reticulum Stress.” <i>ELife</i>, vol. 12, RP89066, eLife Sciences Publications, 2023, doi:<a href=\"https://doi.org/10.7554/eLife.89066\">10.7554/eLife.89066</a>.","ieee":"U. H. Cho and M. Hetzer, “Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress,” <i>eLife</i>, vol. 12. eLife Sciences Publications, 2023.","short":"U.H. Cho, M. Hetzer, ELife 12 (2023).","ama":"Cho UH, Hetzer M. Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress. <i>eLife</i>. 2023;12. doi:<a href=\"https://doi.org/10.7554/eLife.89066\">10.7554/eLife.89066</a>","ista":"Cho UH, Hetzer M. 2023. Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress. eLife. 12, RP89066.","apa":"Cho, U. H., &#38; Hetzer, M. (2023). Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.89066\">https://doi.org/10.7554/eLife.89066</a>"},"publication":"eLife","scopus_import":"1","abstract":[{"text":"During apoptosis, caspases degrade 8 out of ~30 nucleoporins to irreversibly demolish the nuclear pore complex. However, for poorly understood reasons, caspases are also activated during cell differentiation. Here, we show that sublethal activation of caspases during myogenesis results in the transient proteolysis of four peripheral Nups and one transmembrane Nup. ‘Trimmed’ NPCs become nuclear export-defective, and we identified in an unbiased manner several classes of cytoplasmic, plasma membrane, and mitochondrial proteins that rapidly accumulate in the nucleus. NPC trimming by non-apoptotic caspases was also observed in neurogenesis and endoplasmic reticulum stress. Our results suggest that caspases can reversibly modulate nuclear transport activity, which allows them to function as agents of cell differentiation and adaptation at sublethal levels.","lang":"eng"}],"doi":"10.7554/eLife.89066","date_published":"2023-09-04T00:00:00Z","day":"04","month":"09","oa_version":"Published Version","publisher":"eLife Sciences Publications","external_id":{"pmid":["37665327"]},"acknowledgement":"We thank the members of the Hetzer laboratory, Tony Hunter (Salk), Lorenzo Puri (Sanford Burnham Prebys), and Jongmin Kim (Massachusetts General Hospital) for the critical reading of the manuscript; Kenneth Diffenderfer and Aimee Pankonin (Stem Cell Core at the Salk Institute) for help with neurogenesis; Carol Marchetto and Fred Gage (Salk) for providing H9 embryonic stem cells; Lorenzo Puri, Alexandra Sacco, and Luca Caputo (Sanford Burnham Prebys) for helpful discussions and sharing mouse primary myoblasts. This work was supported by a Glenn Foundation for Medical Research Postdoctoral Fellowship in Aging Research (UHC), the NOMIS foundation (MWH), and the National Institutes of Health (R01 NS096786 to MWH and K01 AR080828 to UHC). This work was also supported by the Mass Spectrometry Core of the Salk Institute with funding from NIH-NCI CCSG: P30 014195 and the Helmsley Center for Genomic Medicine. We thank Jolene Diedrich and Antonio Pinto for technical support.","_id":"14315","department":[{"_id":"MaHe"}],"quality_controlled":"1","article_number":"RP89066","pmid":1,"intvolume":"        12","volume":12,"publication_identifier":{"eissn":["2050-084X"]},"article_type":"original","status":"public","ddc":["570"],"type":"journal_article","title":"Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress","file":[{"creator":"dernst","checksum":"db24bf3d595507387b48d3799c33e289","file_size":3703097,"file_id":"14336","content_type":"application/pdf","date_created":"2023-09-15T06:59:10Z","file_name":"2023_eLife_Cho.pdf","access_level":"open_access","relation":"main_file","success":1,"date_updated":"2023-09-15T06:59:10Z"}],"publication_status":"published","fulldoi":"https://doi.org/10.7554/eLife.89066","oa":1,"article_processing_charge":"Yes","has_accepted_license":"1","file_date_updated":"2023-09-15T06:59:10Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"language":[{"iso":"eng"}],"corr_author":"1"},{"day":"23","date_published":"2023-06-23T00:00:00Z","doi":"10.7554/elife.87462","abstract":[{"lang":"eng","text":"The role of nuclear pore complexes (NPCs) in genome organization remains poorly characterized due to technical limitations in probing genome-wide protein-DNA interactions specific to the nuclear periphery. Here, we developed a new sensitive method, NPC-DamID, which combines in vitro reconstitution of nuclear import and DamID technology. The fixation-free method identifies chromatin interactions at the NPCs in intact nuclei from cells and tissues. We found that NPCs are preferentially associated with common and hierarchically arranged super-enhancers (SEs) across multiple cell types. We also uncovered phase-separated condensates at NPCs that compartmentalize and concentrate transcriptional coactivators and structural proteins at SE-regulated genes. Our results support NPCs as anchoring sites for SE regulatory hubs and cell-type-specific transcriptional control."}],"publication_status":"epub_ahead","title":"High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope","fulldoi":"https://doi.org/10.7554/elife.87462","date_updated":"2024-07-31T11:56:25Z","author":[{"full_name":"Tyagi, Swati","last_name":"Tyagi","first_name":"Swati"},{"last_name":"Capitanio","first_name":"Juliana S.","full_name":"Capitanio, Juliana S."},{"first_name":"Jiawei","last_name":"Xu","full_name":"Xu, Jiawei"},{"full_name":"Chen, Fei","first_name":"Fei","last_name":"Chen"},{"first_name":"Rahul","last_name":"Sharma","full_name":"Sharma, Rahul"},{"full_name":"Huang, Jialiang","last_name":"Huang","first_name":"Jialiang"},{"full_name":"HETZER, Martin W","orcid":"0000-0002-2111-992X","first_name":"Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","last_name":"HETZER"}],"status":"public","type":"journal_article","main_file_link":[{"open_access":"1","url":"https://doi.org/10.7554/eLife.87462.1"}],"publication":"eLife","citation":{"ista":"Tyagi S, Capitanio JS, Xu J, Chen F, Sharma R, Huang J, Hetzer M. 2023. High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope. eLife.","ama":"Tyagi S, Capitanio JS, Xu J, et al. High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope. <i>eLife</i>. 2023. doi:<a href=\"https://doi.org/10.7554/elife.87462\">10.7554/elife.87462</a>","apa":"Tyagi, S., Capitanio, J. S., Xu, J., Chen, F., Sharma, R., Huang, J., &#38; Hetzer, M. (2023). High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.87462\">https://doi.org/10.7554/elife.87462</a>","chicago":"Tyagi, Swati, Juliana S. Capitanio, Jiawei Xu, Fei Chen, Rahul Sharma, Jialiang Huang, and Martin Hetzer. “High-Precision Mapping of Nuclear Pore-Chromatin Interactions Reveals New Principles of Genome Organization at the Nuclear Envelope.” <i>ELife</i>. eLife Sciences Publications, 2023. <a href=\"https://doi.org/10.7554/elife.87462\">https://doi.org/10.7554/elife.87462</a>.","mla":"Tyagi, Swati, et al. “High-Precision Mapping of Nuclear Pore-Chromatin Interactions Reveals New Principles of Genome Organization at the Nuclear Envelope.” <i>ELife</i>, eLife Sciences Publications, 2023, doi:<a href=\"https://doi.org/10.7554/elife.87462\">10.7554/elife.87462</a>.","short":"S. Tyagi, J.S. Capitanio, J. Xu, F. Chen, R. Sharma, J. Huang, M. Hetzer, ELife (2023).","ieee":"S. Tyagi <i>et al.</i>, “High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope,” <i>eLife</i>. eLife Sciences Publications, 2023."},"date_created":"2024-01-22T12:21:56Z","year":"2023","corr_author":"1","article_type":"original","article_processing_charge":"Yes","publisher":"eLife Sciences Publications","oa":1,"month":"06","oa_version":"Submitted Version","department":[{"_id":"MaHe"}],"_id":"14868","language":[{"iso":"eng"}],"acknowledgement":"This work was supported by M.H.’s NIH R01 grants (NS096786, GM126829) and Salk Cancer Center Support Grant P30 CA014195. M.H. also received financial support from the W.M. Keck Foundation and the NOMIS Foundation. Further, M.H. received support from the AHA-Allen Initiative in Brain Health and Cognitive Impairment award made jointly through the American Heart Association and The Paul G. Allen Frontiers Group (19PABH134610000).\r\n\r\nS.T. and J.C. were supported by Salk’s Women & Science Awards. S.T. also received financial support from the Hewitt Foundation fellowship, and J.C. is a Paul F. Glenn Biology of Aging fellow. J.H. was supported by the National Natural Science Foundation of China (31871317 and 32070635).\r\n\r\nWe thank Roberta Schulte for assistance with in vitro transport assays, for comments that greatly improved the manuscript, and for helping refine the figures presented in this work. We thank Shefali Krishna for creating the diagram for the NPC-DamID method, for her input on super-resolution microscopy analysis, and her insightful comments on this manuscript. We thank all members of the Hetzer lab for helpful discussions of these research ideas and their thoughtful comments on this manuscript. We are also grateful to Salk’s core facilities for their assistance. Specifically, we thank the Next Generation Sequencing Core (NGS) for sequencing our DamID and RNA NGS libraries, the Advanced Biophotonics Core for assistance with super-resolution microscopy, and the Razavi Newman Integrative Genomics and Bioinformatics Core (IGC) for their input on analysis methods for DamID experiments.","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"date_updated":"2024-10-14T11:14:57Z","author":[{"full_name":"Liu, Jinqiang","last_name":"Liu","first_name":"Jinqiang"},{"orcid":"0000-0002-2111-992X","full_name":"HETZER, Martin W","last_name":"HETZER","first_name":"Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed"}],"publication":"Trends in Cell Biology","citation":{"apa":"Liu, J., &#38; Hetzer, M. (2022). Nuclear pore complex maintenance and implications for age-related diseases. <i>Trends in Cell Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.tcb.2021.10.001\">https://doi.org/10.1016/j.tcb.2021.10.001</a>","ama":"Liu J, Hetzer M. Nuclear pore complex maintenance and implications for age-related diseases. <i>Trends in Cell Biology</i>. 2022;32(3):P216-227. doi:<a href=\"https://doi.org/10.1016/j.tcb.2021.10.001\">10.1016/j.tcb.2021.10.001</a>","ista":"Liu J, Hetzer M. 2022. Nuclear pore complex maintenance and implications for age-related diseases. Trends in Cell Biology. 32(3), P216-227.","short":"J. Liu, M. Hetzer, Trends in Cell Biology 32 (2022) P216-227.","ieee":"J. Liu and M. Hetzer, “Nuclear pore complex maintenance and implications for age-related diseases,” <i>Trends in Cell Biology</i>, vol. 32, no. 3. Elsevier, pp. P216-227, 2022.","mla":"Liu, Jinqiang, and Martin Hetzer. “Nuclear Pore Complex Maintenance and Implications for Age-Related Diseases.” <i>Trends in Cell Biology</i>, vol. 32, no. 3, Elsevier, 2022, pp. P216-227, doi:<a href=\"https://doi.org/10.1016/j.tcb.2021.10.001\">10.1016/j.tcb.2021.10.001</a>.","chicago":"Liu, Jinqiang, and Martin Hetzer. “Nuclear Pore Complex Maintenance and Implications for Age-Related Diseases.” <i>Trends in Cell Biology</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.tcb.2021.10.001\">https://doi.org/10.1016/j.tcb.2021.10.001</a>."},"year":"2022","date_created":"2022-04-07T07:43:01Z","date_published":"2022-03-01T00:00:00Z","day":"01","doi":"10.1016/j.tcb.2021.10.001","scopus_import":"1","abstract":[{"text":"Nuclear pore complexes (NPCs) bridge the nucleus and the cytoplasm and are indispensable for crucial cellular activities, such as bidirectional molecular trafficking and gene transcription regulation. The discovery of long-lived proteins (LLPs) in NPCs from postmitotic cells raises the exciting possibility that the maintenance of NPC integrity might play an inherent role in lifelong cell function. Age-dependent deterioration of NPCs and loss of nuclear integrity have been linked to age-related decline in postmitotic cell function and degenerative diseases. In this review, we discuss our current understanding of NPC maintenance in proliferating and postmitotic cells, and how malfunction of nucleoporins (Nups) might contribute to the pathogenesis of various neurodegenerative and cardiovascular diseases.","lang":"eng"}],"external_id":{"pmid":["34782239"]},"publisher":"Elsevier","month":"03","oa_version":"None","_id":"11051","pmid":1,"extern":"1","issue":"3","quality_controlled":"1","publication_identifier":{"issn":["0962-8924"]},"article_type":"review","volume":32,"intvolume":"        32","status":"public","type":"journal_article","publication_status":"published","title":"Nuclear pore complex maintenance and implications for age-related diseases","fulldoi":"https://doi.org/10.1016/j.tcb.2021.10.001","article_processing_charge":"No","language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","page":"P216-227","keyword":["Cell Biology"]},{"publication_status":"published","title":"Identification of long-lived proteins in the mitochondria reveals increased stability of the electron transport chain","fulldoi":"https://doi.org/10.1016/j.devcel.2021.10.008","status":"public","type":"journal_article","keyword":["Developmental Biology","Cell Biology","General Biochemistry","Genetics and Molecular Biology","Molecular Biology"],"article_processing_charge":"No","language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","page":"P2952-2965.e9","scopus_import":"1","abstract":[{"text":"In order to combat molecular damage, most cellular proteins undergo rapid turnover. We have previously identified large nuclear protein assemblies that can persist for years in post-mitotic tissues and are subject to age-related decline. Here, we report that mitochondria can be long lived in the mouse brain and reveal that specific mitochondrial proteins have half-lives longer than the average proteome. These mitochondrial long-lived proteins (mitoLLPs) are core components of the electron transport chain (ETC) and display increased longevity in respiratory supercomplexes. We find that COX7C, a mitoLLP that forms a stable contact site between complexes I and IV, is required for complex IV and supercomplex assembly. Remarkably, even upon depletion of COX7C transcripts, ETC function is maintained for days, effectively uncoupling mitochondrial function from ongoing transcription of its mitoLLPs. Our results suggest that modulating protein longevity within the ETC is critical for mitochondrial proteome maintenance and the robustness of mitochondrial function.","lang":"eng"}],"day":"08","date_published":"2021-11-08T00:00:00Z","doi":"10.1016/j.devcel.2021.10.008","author":[{"full_name":"Krishna, Shefali","last_name":"Krishna","first_name":"Shefali"},{"last_name":"Arrojo e Drigo","first_name":"Rafael","full_name":"Arrojo e Drigo, Rafael"},{"last_name":"Capitanio","first_name":"Juliana S.","full_name":"Capitanio, Juliana S."},{"first_name":"Ranjan","last_name":"Ramachandra","full_name":"Ramachandra, Ranjan"},{"first_name":"Mark","last_name":"Ellisman","full_name":"Ellisman, Mark"},{"last_name":"HETZER","first_name":"Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","orcid":"0000-0002-2111-992X","full_name":"HETZER, Martin W"}],"date_updated":"2025-12-15T10:01:56Z","citation":{"ama":"Krishna S, Arrojo e Drigo R, Capitanio JS, Ramachandra R, Ellisman M, Hetzer M. Identification of long-lived proteins in the mitochondria reveals increased stability of the electron transport chain. <i>Developmental Cell</i>. 2021;56(21):P2952-2965.e9. doi:<a href=\"https://doi.org/10.1016/j.devcel.2021.10.008\">10.1016/j.devcel.2021.10.008</a>","ista":"Krishna S, Arrojo e Drigo R, Capitanio JS, Ramachandra R, Ellisman M, Hetzer M. 2021. Identification of long-lived proteins in the mitochondria reveals increased stability of the electron transport chain. Developmental Cell. 56(21), P2952–2965.e9.","apa":"Krishna, S., Arrojo e Drigo, R., Capitanio, J. S., Ramachandra, R., Ellisman, M., &#38; Hetzer, M. (2021). Identification of long-lived proteins in the mitochondria reveals increased stability of the electron transport chain. <i>Developmental Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.devcel.2021.10.008\">https://doi.org/10.1016/j.devcel.2021.10.008</a>","chicago":"Krishna, Shefali, Rafael Arrojo e Drigo, Juliana S. Capitanio, Ranjan Ramachandra, Mark Ellisman, and Martin Hetzer. “Identification of Long-Lived Proteins in the Mitochondria Reveals Increased Stability of the Electron Transport Chain.” <i>Developmental Cell</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.devcel.2021.10.008\">https://doi.org/10.1016/j.devcel.2021.10.008</a>.","mla":"Krishna, Shefali, et al. “Identification of Long-Lived Proteins in the Mitochondria Reveals Increased Stability of the Electron Transport Chain.” <i>Developmental Cell</i>, vol. 56, no. 21, Elsevier, 2021, p. P2952–2965.e9, doi:<a href=\"https://doi.org/10.1016/j.devcel.2021.10.008\">10.1016/j.devcel.2021.10.008</a>.","ieee":"S. Krishna, R. Arrojo e Drigo, J. S. Capitanio, R. Ramachandra, M. Ellisman, and M. Hetzer, “Identification of long-lived proteins in the mitochondria reveals increased stability of the electron transport chain,” <i>Developmental Cell</i>, vol. 56, no. 21. Elsevier, p. P2952–2965.e9, 2021.","short":"S. Krishna, R. Arrojo e Drigo, J.S. Capitanio, R. Ramachandra, M. Ellisman, M. Hetzer, Developmental Cell 56 (2021) P2952–2965.e9."},"date_created":"2022-04-07T07:43:14Z","year":"2021","publication":"Developmental Cell","quality_controlled":"1","issue":"21","extern":"1","pmid":1,"intvolume":"        56","publication_identifier":{"issn":["1534-5807"]},"article_type":"original","volume":56,"publisher":"Elsevier","month":"11","oa_version":"None","external_id":{"pmid":["34715012"]},"department":[{"_id":"MaHe"}],"_id":"11052"},{"keyword":["Geriatrics and Gerontology","Aging"],"article_processing_charge":"No","oa":1,"language":[{"iso":"eng"}],"user_id":"72615eeb-f1f3-11ec-aa25-d4573ddc34fd","page":"2139-2148","publication_status":"published","title":"The San Diego Nathan Shock Center: Tackling the heterogeneity of aging","fulldoi":"https://doi.org/10.1007/s11357-021-00426-x","status":"public","type":"journal_article","extern":"1","pmid":1,"issue":"5","quality_controlled":"1","publication_identifier":{"issn":["2509-2715","2509-2723"]},"article_type":"original","volume":43,"intvolume":"        43","external_id":{"pmid":["34370163"]},"publisher":"Springer Nature","oa_version":"Published Version","month":"10","_id":"11053","day":"01","date_published":"2021-10-01T00:00:00Z","doi":"10.1007/s11357-021-00426-x","abstract":[{"text":"Understanding basic mechanisms of aging holds great promise for developing interventions that prevent or delay many age-related declines and diseases simultaneously to increase human healthspan. However, a major confounding factor in aging research is the heterogeneity of the aging process itself. At the organismal level, it is clear that chronological age does not always predict biological age or susceptibility to frailty or pathology. While genetics and environment are major factors driving variable rates of aging, additional complexity arises because different organs, tissues, and cell types are intrinsically heterogeneous and exhibit different aging trajectories normally or in response to the stresses of the aging process (e.g., damage accumulation). Tackling the heterogeneity of aging requires new and specialized tools (e.g., single-cell analyses, mass spectrometry-based approaches, and advanced imaging) to identify novel signatures of aging across scales. Cutting-edge computational approaches are then needed to integrate these disparate datasets and elucidate network interactions between known aging hallmarks. There is also a need for improved, human cell-based models of aging to ensure that basic research findings are relevant to human aging and healthspan interventions. The San Diego Nathan Shock Center (SD-NSC) provides access to cutting-edge scientific resources to facilitate the study of the heterogeneity of aging in general and to promote the use of novel human cell models of aging. The center also has a robust Research Development Core that funds pilot projects on the heterogeneity of aging and organizes innovative training activities, including workshops and a personalized mentoring program, to help investigators new to the aging field succeed. Finally, the SD-NSC participates in outreach activities to educate the general community about the importance of aging research and promote the need for basic biology of aging research in particular.","lang":"eng"}],"scopus_import":"1","date_updated":"2022-07-18T08:27:24Z","author":[{"full_name":"Shadel, Gerald S.","first_name":"Gerald S.","last_name":"Shadel"},{"full_name":"Adams, Peter D.","last_name":"Adams","first_name":"Peter D."},{"last_name":"Berggren","first_name":"W. Travis","full_name":"Berggren, W. Travis"},{"last_name":"Diedrich","first_name":"Jolene K.","full_name":"Diedrich, Jolene K."},{"full_name":"Diffenderfer, Kenneth E.","last_name":"Diffenderfer","first_name":"Kenneth E."},{"full_name":"Gage, Fred H.","first_name":"Fred H.","last_name":"Gage"},{"full_name":"Hah, Nasun","last_name":"Hah","first_name":"Nasun"},{"full_name":"Hansen, Malene","last_name":"Hansen","first_name":"Malene"},{"id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","first_name":"Martin W","last_name":"HETZER","full_name":"HETZER, Martin W","orcid":"0000-0002-2111-992X"},{"last_name":"Molina","first_name":"Anthony J. A.","full_name":"Molina, Anthony J. A."},{"last_name":"Manor","first_name":"Uri","full_name":"Manor, Uri"},{"first_name":"Kurt","last_name":"Marek","full_name":"Marek, Kurt"},{"full_name":"O’Keefe, David D.","last_name":"O’Keefe","first_name":"David D."},{"last_name":"Pinto","first_name":"Antonio F. M.","full_name":"Pinto, Antonio F. M."},{"last_name":"Sacco","first_name":"Alessandra","full_name":"Sacco, Alessandra"},{"first_name":"Tatyana O.","last_name":"Sharpee","full_name":"Sharpee, Tatyana O."},{"full_name":"Shokriev, Maxim N.","last_name":"Shokriev","first_name":"Maxim N."},{"first_name":"Stefania","last_name":"Zambetti","full_name":"Zambetti, Stefania"}],"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599742/","open_access":"1"}],"publication":"GeroScience","citation":{"chicago":"Shadel, Gerald S., Peter D. Adams, W. Travis Berggren, Jolene K. Diedrich, Kenneth E. Diffenderfer, Fred H. Gage, Nasun Hah, et al. “The San Diego Nathan Shock Center: Tackling the Heterogeneity of Aging.” <i>GeroScience</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1007/s11357-021-00426-x\">https://doi.org/10.1007/s11357-021-00426-x</a>.","mla":"Shadel, Gerald S., et al. “The San Diego Nathan Shock Center: Tackling the Heterogeneity of Aging.” <i>GeroScience</i>, vol. 43, no. 5, Springer Nature, 2021, pp. 2139–48, doi:<a href=\"https://doi.org/10.1007/s11357-021-00426-x\">10.1007/s11357-021-00426-x</a>.","short":"G.S. Shadel, P.D. Adams, W.T. Berggren, J.K. Diedrich, K.E. Diffenderfer, F.H. Gage, N. Hah, M. Hansen, M. Hetzer, A.J.A. Molina, U. Manor, K. Marek, D.D. O’Keefe, A.F.M. Pinto, A. Sacco, T.O. Sharpee, M.N. Shokriev, S. Zambetti, GeroScience 43 (2021) 2139–2148.","ieee":"G. S. Shadel <i>et al.</i>, “The San Diego Nathan Shock Center: Tackling the heterogeneity of aging,” <i>GeroScience</i>, vol. 43, no. 5. Springer Nature, pp. 2139–2148, 2021.","ista":"Shadel GS, Adams PD, Berggren WT, Diedrich JK, Diffenderfer KE, Gage FH, Hah N, Hansen M, Hetzer M, Molina AJA, Manor U, Marek K, O’Keefe DD, Pinto AFM, Sacco A, Sharpee TO, Shokriev MN, Zambetti S. 2021. The San Diego Nathan Shock Center: Tackling the heterogeneity of aging. GeroScience. 43(5), 2139–2148.","ama":"Shadel GS, Adams PD, Berggren WT, et al. The San Diego Nathan Shock Center: Tackling the heterogeneity of aging. <i>GeroScience</i>. 2021;43(5):2139-2148. doi:<a href=\"https://doi.org/10.1007/s11357-021-00426-x\">10.1007/s11357-021-00426-x</a>","apa":"Shadel, G. S., Adams, P. D., Berggren, W. T., Diedrich, J. K., Diffenderfer, K. E., Gage, F. H., … Zambetti, S. (2021). The San Diego Nathan Shock Center: Tackling the heterogeneity of aging. <i>GeroScience</i>. Springer Nature. <a href=\"https://doi.org/10.1007/s11357-021-00426-x\">https://doi.org/10.1007/s11357-021-00426-x</a>"},"year":"2021","date_created":"2022-04-07T07:43:25Z"},{"author":[{"last_name":"Cho","first_name":"Ukrae H.","full_name":"Cho, Ukrae H."},{"last_name":"HETZER","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","first_name":"Martin W","orcid":"0000-0002-2111-992X","full_name":"HETZER, Martin W"}],"date_updated":"2024-10-14T11:15:26Z","date_created":"2022-04-07T07:43:36Z","year":"2020","citation":{"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>","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.","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>","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>.","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.","short":"U.H. Cho, M. Hetzer, Neuron 106 (2020) 899–911.","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>."},"main_file_link":[{"url":"https://doi.org/10.1016/j.neuron.2020.05.031","open_access":"1"}],"publication":"Neuron","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."}],"scopus_import":"1","doi":"10.1016/j.neuron.2020.05.031","date_published":"2020-06-17T00:00:00Z","day":"17","oa_version":"Published Version","month":"06","publisher":"Elsevier","external_id":{"pmid":["32553207"]},"_id":"11054","quality_controlled":"1","extern":"1","pmid":1,"issue":"6","intvolume":"       106","volume":106,"publication_identifier":{"issn":["0896-6273"]},"article_type":"review","status":"public","type":"journal_article","title":"Nuclear periphery takes center stage: The role of nuclear pore complexes in cell identity and aging","publication_status":"published","fulldoi":"https://doi.org/10.1016/j.neuron.2020.05.031","oa":1,"article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","page":"899-911","language":[{"iso":"eng"}],"keyword":["General Neuroscience"]},{"external_id":{"pmid":["32896271"]},"month":"09","oa_version":"Published Version","publisher":"eLife Sciences Publications","_id":"11055","pmid":1,"extern":"1","article_number":"e54383","quality_controlled":"1","volume":9,"publication_identifier":{"issn":["2050-084X"]},"article_type":"original","intvolume":"         9","date_updated":"2024-10-14T11:17:02Z","author":[{"last_name":"Bersini","first_name":"Simone","full_name":"Bersini, Simone"},{"full_name":"Schulte, Roberta","first_name":"Roberta","last_name":"Schulte"},{"last_name":"Huang","first_name":"Ling","full_name":"Huang, Ling"},{"first_name":"Hannah","last_name":"Tsai","full_name":"Tsai, Hannah"},{"last_name":"HETZER","first_name":"Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","orcid":"0000-0002-2111-992X","full_name":"HETZER, Martin W"}],"publication":"eLife","year":"2020","date_created":"2022-04-07T07:43:48Z","citation":{"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.","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>","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>.","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.","short":"S. Bersini, R. Schulte, L. Huang, H. Tsai, M. Hetzer, ELife 9 (2020)."},"doi":"10.7554/elife.54383","date_published":"2020-09-08T00:00:00Z","day":"08","scopus_import":"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"}],"file_date_updated":"2022-04-08T06:53:10Z","article_processing_charge":"No","has_accepted_license":"1","oa":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"language":[{"iso":"eng"}],"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"status":"public","type":"journal_article","ddc":["570"],"title":"Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome","file":[{"file_id":"11132","file_size":4399825,"creator":"dernst","checksum":"f8b3821349a194050be02570d8fe7d4b","success":1,"date_updated":"2022-04-08T06:53:10Z","relation":"main_file","date_created":"2022-04-08T06:53:10Z","content_type":"application/pdf","access_level":"open_access","file_name":"2020_eLife_Bersini.pdf"}],"publication_status":"published","fulldoi":"https://doi.org/10.7554/elife.54383"},{"doi":"10.1002/adbi.202000044","day":"01","date_published":"2020-05-01T00:00:00Z","scopus_import":"1","abstract":[{"text":"Aging of the circulatory system correlates with the pathogenesis of a large spectrum of diseases. However, it is largely unknown which factors drive the age-dependent or pathological decline of the vasculature and how vascular defects relate to tissue aging. The goal of the study is to design a multianalytical approach to identify how the cellular microenvironment (i.e., fibroblasts) and serum from healthy donors of different ages or Alzheimer disease (AD) patients can modulate the functionality of organ-specific vascular endothelial cells (VECs). Long-living human microvascular networks embedding VECs and fibroblasts from skin biopsies are generated. RNA-seq, secretome analyses, and microfluidic assays demonstrate that fibroblasts from young donors restore the functionality of aged endothelial cells, an effect also achieved by serum from young donors. New biomarkers of vascular aging are validated in human biopsies and it is shown that young serum induces angiopoietin-like-4, which can restore compromised vascular barriers. This strategy is then employed to characterize transcriptional/functional changes induced on the blood–brain barrier by AD serum, demonstrating the importance of PTP4A3 in the regulation of permeability. Features of vascular degeneration during aging and AD are recapitulated, and a tool to identify novel biomarkers that can be exploited to develop future therapeutics modulating vascular function is established.","lang":"eng"}],"date_updated":"2024-10-14T11:18:07Z","author":[{"full_name":"Bersini, Simone","first_name":"Simone","last_name":"Bersini"},{"first_name":"Rafael","last_name":"Arrojo e Drigo","full_name":"Arrojo e Drigo, Rafael"},{"full_name":"Huang, Ling","last_name":"Huang","first_name":"Ling"},{"first_name":"Maxim N.","last_name":"Shokhirev","full_name":"Shokhirev, Maxim N."},{"full_name":"HETZER, Martin W","orcid":"0000-0002-2111-992X","first_name":"Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","last_name":"HETZER"}],"publication":"Advanced Biosystems","date_created":"2022-04-07T07:43:57Z","year":"2020","citation":{"apa":"Bersini, S., Arrojo e Drigo, R., Huang, L., Shokhirev, M. N., &#38; Hetzer, M. (2020). Transcriptional and functional changes of the human microvasculature during physiological aging and Alzheimer disease. <i>Advanced Biosystems</i>. Wiley. <a href=\"https://doi.org/10.1002/adbi.202000044\">https://doi.org/10.1002/adbi.202000044</a>","ama":"Bersini S, Arrojo e Drigo R, Huang L, Shokhirev MN, Hetzer M. Transcriptional and functional changes of the human microvasculature during physiological aging and Alzheimer disease. <i>Advanced Biosystems</i>. 2020;4(5). doi:<a href=\"https://doi.org/10.1002/adbi.202000044\">10.1002/adbi.202000044</a>","ista":"Bersini S, Arrojo e Drigo R, Huang L, Shokhirev MN, Hetzer M. 2020. Transcriptional and functional changes of the human microvasculature during physiological aging and Alzheimer disease. Advanced Biosystems. 4(5), 2000044.","mla":"Bersini, Simone, et al. “Transcriptional and Functional Changes of the Human Microvasculature during Physiological Aging and Alzheimer Disease.” <i>Advanced Biosystems</i>, vol. 4, no. 5, 2000044, Wiley, 2020, doi:<a href=\"https://doi.org/10.1002/adbi.202000044\">10.1002/adbi.202000044</a>.","short":"S. Bersini, R. Arrojo e Drigo, L. Huang, M.N. Shokhirev, M. Hetzer, Advanced Biosystems 4 (2020).","ieee":"S. Bersini, R. Arrojo e Drigo, L. Huang, M. N. Shokhirev, and M. Hetzer, “Transcriptional and functional changes of the human microvasculature during physiological aging and Alzheimer disease,” <i>Advanced Biosystems</i>, vol. 4, no. 5. Wiley, 2020.","chicago":"Bersini, Simone, Rafael Arrojo e Drigo, Ling Huang, Maxim N. Shokhirev, and Martin Hetzer. “Transcriptional and Functional Changes of the Human Microvasculature during Physiological Aging and Alzheimer Disease.” <i>Advanced Biosystems</i>. Wiley, 2020. <a href=\"https://doi.org/10.1002/adbi.202000044\">https://doi.org/10.1002/adbi.202000044</a>."},"pmid":1,"issue":"5","article_number":"2000044","extern":"1","quality_controlled":"1","volume":4,"publication_identifier":{"issn":["2366-7478","2366-7478"]},"article_type":"original","intvolume":"         4","external_id":{"pmid":["32402127"]},"oa_version":"Published Version","month":"05","publisher":"Wiley","_id":"11056","title":"Transcriptional and functional changes of the human microvasculature during physiological aging and Alzheimer disease","file":[{"access_level":"open_access","file_name":"2020_AdvancedBiosystems_Bersini.pdf","date_created":"2022-04-08T07:06:05Z","content_type":"application/pdf","relation":"main_file","success":1,"date_updated":"2022-04-08T07:06:05Z","checksum":"5584d9a1609812dc75c02ce1e35d2ec0","creator":"dernst","file_id":"11134","file_size":2490829}],"publication_status":"published","fulldoi":"https://doi.org/10.1002/adbi.202000044","status":"public","type":"journal_article","ddc":["570"],"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","keyword":["General Biochemistry","Genetics and Molecular Biology","Biomedical Engineering","Biomaterials"],"article_processing_charge":"No","has_accepted_license":"1","file_date_updated":"2022-04-08T07:06:05Z","oa":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"language":[{"iso":"eng"}]},{"fulldoi":"https://doi.org/10.1101/gad.335794.119","publication_status":"published","file":[{"checksum":"84e92d40e67936c739628315c238daf9","creator":"dernst","file_id":"11136","file_size":4406772,"access_level":"open_access","file_name":"2020_GenesDevelopment_Kang.pdf","date_created":"2022-04-08T07:12:33Z","content_type":"application/pdf","date_updated":"2022-04-08T07:12:33Z","relation":"main_file","success":1}],"title":"Dynamic regulation of histone modifications and long-range chromosomal interactions during postmitotic transcriptional reactivation","ddc":["570"],"type":"journal_article","status":"public","keyword":["Developmental Biology","Genetics"],"language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","page":"913-930","oa":1,"file_date_updated":"2022-04-08T07:12:33Z","has_accepted_license":"1","article_processing_charge":"No","abstract":[{"text":"During mitosis, transcription of genomic DNA is dramatically reduced, before it is reactivated during nuclear reformation in anaphase/telophase. Many aspects of the underlying principles that mediate transcriptional memory and reactivation in the daughter cells remain unclear. Here, we used ChIP-seq on synchronized cells at different stages after mitosis to generate genome-wide maps of histone modifications. Combined with EU-RNA-seq and Hi-C analyses, we found that during prometaphase, promoters, enhancers, and insulators retain H3K4me3 and H3K4me1, while losing H3K27ac. Enhancers globally retaining mitotic H3K4me1 or locally retaining mitotic H3K27ac are associated with cell type-specific genes and their transcription factors for rapid transcriptional activation. As cells exit mitosis, promoters regain H3K27ac, which correlates with transcriptional reactivation. Insulators also gain H3K27ac and CCCTC-binding factor (CTCF) in anaphase/telophase. This increase of H3K27ac in anaphase/telophase is required for posttranscriptional activation and may play a role in the establishment of topologically associating domains (TADs). Together, our results suggest that the genome is reorganized in a sequential order, in which histone methylations occur first in prometaphase, histone acetylation, and CTCF in anaphase/telophase, transcription in cytokinesis, and long-range chromatin interactions in early G1. We thus provide insights into the histone modification landscape that allows faithful reestablishment of the transcriptional program and TADs during cell division.","lang":"eng"}],"scopus_import":"1","day":"28","date_published":"2020-04-28T00:00:00Z","doi":"10.1101/gad.335794.119","citation":{"ama":"Kang H, Shokhirev MN, Xu Z, Chandran S, Dixon JR, Hetzer M. Dynamic regulation of histone modifications and long-range chromosomal interactions during postmitotic transcriptional reactivation. <i>Genes &#38; Development</i>. 2020;34(13-14):913-930. doi:<a href=\"https://doi.org/10.1101/gad.335794.119\">10.1101/gad.335794.119</a>","ista":"Kang H, Shokhirev MN, Xu Z, Chandran S, Dixon JR, Hetzer M. 2020. Dynamic regulation of histone modifications and long-range chromosomal interactions during postmitotic transcriptional reactivation. Genes &#38; Development. 34(13–14), 913–930.","apa":"Kang, H., Shokhirev, M. N., Xu, Z., Chandran, S., Dixon, J. R., &#38; Hetzer, M. (2020). Dynamic regulation of histone modifications and long-range chromosomal interactions during postmitotic transcriptional reactivation. <i>Genes &#38; Development</i>. Cold Spring Harbor Laboratory Press. <a href=\"https://doi.org/10.1101/gad.335794.119\">https://doi.org/10.1101/gad.335794.119</a>","chicago":"Kang, Hyeseon, Maxim N. Shokhirev, Zhichao Xu, Sahaana Chandran, Jesse R. Dixon, and Martin Hetzer. “Dynamic Regulation of Histone Modifications and Long-Range Chromosomal Interactions during Postmitotic Transcriptional Reactivation.” <i>Genes &#38; Development</i>. Cold Spring Harbor Laboratory Press, 2020. <a href=\"https://doi.org/10.1101/gad.335794.119\">https://doi.org/10.1101/gad.335794.119</a>.","mla":"Kang, Hyeseon, et al. “Dynamic Regulation of Histone Modifications and Long-Range Chromosomal Interactions during Postmitotic Transcriptional Reactivation.” <i>Genes &#38; Development</i>, vol. 34, no. 13–14, Cold Spring Harbor Laboratory Press, 2020, pp. 913–30, doi:<a href=\"https://doi.org/10.1101/gad.335794.119\">10.1101/gad.335794.119</a>.","short":"H. Kang, M.N. Shokhirev, Z. Xu, S. Chandran, J.R. Dixon, M. Hetzer, Genes &#38; Development 34 (2020) 913–930.","ieee":"H. Kang, M. N. Shokhirev, Z. Xu, S. Chandran, J. R. Dixon, and M. Hetzer, “Dynamic regulation of histone modifications and long-range chromosomal interactions during postmitotic transcriptional reactivation,” <i>Genes &#38; Development</i>, vol. 34, no. 13–14. Cold Spring Harbor Laboratory Press, pp. 913–930, 2020."},"date_created":"2022-04-07T07:44:09Z","year":"2020","publication":"Genes & Development","author":[{"last_name":"Kang","first_name":"Hyeseon","full_name":"Kang, Hyeseon"},{"full_name":"Shokhirev, Maxim N.","last_name":"Shokhirev","first_name":"Maxim N."},{"first_name":"Zhichao","last_name":"Xu","full_name":"Xu, Zhichao"},{"full_name":"Chandran, Sahaana","first_name":"Sahaana","last_name":"Chandran"},{"last_name":"Dixon","first_name":"Jesse R.","full_name":"Dixon, Jesse R."},{"full_name":"HETZER, Martin W","orcid":"0000-0002-2111-992X","first_name":"Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","last_name":"HETZER"}],"date_updated":"2024-10-14T11:18:25Z","intvolume":"        34","publication_identifier":{"issn":["0890-9369","1549-5477"]},"article_type":"original","volume":34,"quality_controlled":"1","issue":"13-14","pmid":1,"extern":"1","_id":"11057","publisher":"Cold Spring Harbor Laboratory Press","oa_version":"Published Version","month":"04","external_id":{"pmid":["32499403"]}},{"keyword":["Health","Toxicology and Mutagenesis","Plant Science","Biochemistry","Genetics and Molecular Biology (miscellaneous)","Ecology"],"language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"has_accepted_license":"1","article_processing_charge":"No","file_date_updated":"2022-04-08T07:33:01Z","fulldoi":"https://doi.org/10.26508/lsa.201900623","publication_status":"published","title":"Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling","file":[{"checksum":"3bf33e7e93bef7823287807206b69b38","creator":"dernst","file_size":2653960,"file_id":"11137","access_level":"open_access","file_name":"2020_LifeScienceAlliance_Bersini.pdf","date_created":"2022-04-08T07:33:01Z","content_type":"application/pdf","success":1,"date_updated":"2022-04-08T07:33:01Z","relation":"main_file"}],"ddc":["570"],"type":"journal_article","status":"public","intvolume":"         3","article_type":"original","publication_identifier":{"issn":["2575-1077"]},"volume":3,"quality_controlled":"1","pmid":1,"issue":"1","article_number":"e201900623","extern":"1","_id":"11058","publisher":"Life Science Alliance","oa_version":"Published Version","month":"01","external_id":{"pmid":["31959624"]},"scopus_import":"1","abstract":[{"text":"Nucleoporin 93 (Nup93) expression inversely correlates with the survival of triple-negative breast cancer patients. However, our knowledge of Nup93 function in breast cancer besides its role as structural component of the nuclear pore complex is not understood. Combination of functional assays and genetic analyses suggested that chromatin interaction of Nup93 partially modulates the expression of genes associated with actin cytoskeleton remodeling and epithelial to mesenchymal transition, resulting in impaired invasion of triple-negative, claudin-low breast cancer cells. Nup93 depletion induced stress fiber formation associated with reduced cell migration/proliferation and impaired expression of mesenchymal-like genes. Silencing LIMCH1, a gene responsible for actin cytoskeleton remodeling and up-regulated upon Nup93 depletion, partially restored the invasive phenotype of cancer cells. Loss of Nup93 led to significant defects in tumor establishment/propagation in vivo, whereas patient samples revealed that high Nup93 and low LIMCH1 expression correlate with late tumor stage. Our approach identified Nup93 as contributor of triple-negative, claudin-low breast cancer cell invasion and paves the way to study the role of nuclear envelope proteins during breast cancer tumorigenesis.","lang":"eng"}],"day":"01","date_published":"2020-01-01T00:00:00Z","doi":"10.26508/lsa.201900623","citation":{"ista":"Bersini S, Lytle NK, Schulte R, Huang L, Wahl GM, Hetzer M. 2020. Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling. Life Science Alliance. 3(1), e201900623.","ama":"Bersini S, Lytle NK, Schulte R, Huang L, Wahl GM, Hetzer M. Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling. <i>Life Science Alliance</i>. 2020;3(1). doi:<a href=\"https://doi.org/10.26508/lsa.201900623\">10.26508/lsa.201900623</a>","apa":"Bersini, S., Lytle, N. K., Schulte, R., Huang, L., Wahl, G. M., &#38; Hetzer, M. (2020). Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling. <i>Life Science Alliance</i>. Life Science Alliance. <a href=\"https://doi.org/10.26508/lsa.201900623\">https://doi.org/10.26508/lsa.201900623</a>","chicago":"Bersini, Simone, Nikki K Lytle, Roberta Schulte, Ling Huang, Geoffrey M Wahl, and Martin Hetzer. “Nup93 Regulates Breast Tumor Growth by Modulating Cell Proliferation and Actin Cytoskeleton Remodeling.” <i>Life Science Alliance</i>. Life Science Alliance, 2020. <a href=\"https://doi.org/10.26508/lsa.201900623\">https://doi.org/10.26508/lsa.201900623</a>.","ieee":"S. Bersini, N. K. Lytle, R. Schulte, L. Huang, G. M. Wahl, and M. Hetzer, “Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling,” <i>Life Science Alliance</i>, vol. 3, no. 1. Life Science Alliance, 2020.","short":"S. Bersini, N.K. Lytle, R. Schulte, L. Huang, G.M. Wahl, M. Hetzer, Life Science Alliance 3 (2020).","mla":"Bersini, Simone, et al. “Nup93 Regulates Breast Tumor Growth by Modulating Cell Proliferation and Actin Cytoskeleton Remodeling.” <i>Life Science Alliance</i>, vol. 3, no. 1, e201900623, Life Science Alliance, 2020, doi:<a href=\"https://doi.org/10.26508/lsa.201900623\">10.26508/lsa.201900623</a>."},"date_created":"2022-04-07T07:44:18Z","year":"2020","publication":"Life Science Alliance","author":[{"full_name":"Bersini, Simone","last_name":"Bersini","first_name":"Simone"},{"last_name":"Lytle","first_name":"Nikki K","full_name":"Lytle, Nikki K"},{"first_name":"Roberta","last_name":"Schulte","full_name":"Schulte, Roberta"},{"last_name":"Huang","first_name":"Ling","full_name":"Huang, Ling"},{"full_name":"Wahl, Geoffrey M","last_name":"Wahl","first_name":"Geoffrey M"},{"full_name":"HETZER, Martin W","orcid":"0000-0002-2111-992X","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","first_name":"Martin W","last_name":"HETZER"}],"date_updated":"2024-10-14T11:18:41Z"},{"abstract":[{"text":"The genome is packaged and organized nonrandomly within the 3D space of the nucleus to promote efficient gene expression and to faithfully maintain silencing of heterochromatin. The genome is enclosed within the nucleus by the nuclear envelope membrane, which contains a set of proteins that actively participate in chromatin organization and gene regulation. Technological advances are providing views of genome organization at unprecedented resolution and are beginning to reveal the ways that cells co-opt the structures of the nuclear periphery for nuclear organization and gene regulation. These genome regulatory roles of proteins of the nuclear periphery have important influences on development, disease and ageing.","lang":"eng"}],"scopus_import":"1","day":"01","date_published":"2019-01-01T00:00:00Z","doi":"10.1038/s41576-018-0063-5","citation":{"ista":"Buchwalter A, Kaneshiro JM, Hetzer M. 2019. Coaching from the sidelines: The nuclear periphery in genome regulation. Nature Reviews Genetics. 20(1), 39–50.","ama":"Buchwalter A, Kaneshiro JM, Hetzer M. Coaching from the sidelines: The nuclear periphery in genome regulation. <i>Nature Reviews Genetics</i>. 2019;20(1):39-50. doi:<a href=\"https://doi.org/10.1038/s41576-018-0063-5\">10.1038/s41576-018-0063-5</a>","apa":"Buchwalter, A., Kaneshiro, J. M., &#38; Hetzer, M. (2019). Coaching from the sidelines: The nuclear periphery in genome regulation. <i>Nature Reviews Genetics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41576-018-0063-5\">https://doi.org/10.1038/s41576-018-0063-5</a>","chicago":"Buchwalter, Abigail, Jeanae M. Kaneshiro, and Martin Hetzer. “Coaching from the Sidelines: The Nuclear Periphery in Genome Regulation.” <i>Nature Reviews Genetics</i>. Springer Nature, 2019. <a href=\"https://doi.org/10.1038/s41576-018-0063-5\">https://doi.org/10.1038/s41576-018-0063-5</a>.","mla":"Buchwalter, Abigail, et al. “Coaching from the Sidelines: The Nuclear Periphery in Genome Regulation.” <i>Nature Reviews Genetics</i>, vol. 20, no. 1, Springer Nature, 2019, pp. 39–50, doi:<a href=\"https://doi.org/10.1038/s41576-018-0063-5\">10.1038/s41576-018-0063-5</a>.","ieee":"A. Buchwalter, J. M. Kaneshiro, and M. Hetzer, “Coaching from the sidelines: The nuclear periphery in genome regulation,” <i>Nature Reviews Genetics</i>, vol. 20, no. 1. Springer Nature, pp. 39–50, 2019.","short":"A. Buchwalter, J.M. Kaneshiro, M. Hetzer, Nature Reviews Genetics 20 (2019) 39–50."},"year":"2019","date_created":"2022-04-07T07:44:45Z","publication":"Nature Reviews Genetics","author":[{"full_name":"Buchwalter, Abigail","first_name":"Abigail","last_name":"Buchwalter"},{"full_name":"Kaneshiro, Jeanae M.","last_name":"Kaneshiro","first_name":"Jeanae M."},{"full_name":"HETZER, Martin W","orcid":"0000-0002-2111-992X","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","first_name":"Martin W","last_name":"HETZER"}],"date_updated":"2024-10-14T11:18:54Z","intvolume":"        20","article_type":"review","publication_identifier":{"eissn":["1471-0064"],"issn":["1471-0056"]},"volume":20,"quality_controlled":"1","extern":"1","pmid":1,"issue":"1","_id":"11059","publisher":"Springer Nature","oa_version":"None","month":"01","external_id":{"pmid":["30356165"]},"fulldoi":"https://doi.org/10.1038/s41576-018-0063-5","publication_status":"published","title":"Coaching from the sidelines: The nuclear periphery in genome regulation","type":"journal_article","status":"public","keyword":["Genetics (clinical)","Genetics","Molecular Biology"],"language":[{"iso":"eng"}],"page":"39-50","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No"},{"related_material":{"record":[{"id":"13079","status":"public","relation":"research_data"}]},"oa":1,"has_accepted_license":"1","article_processing_charge":"No","file_date_updated":"2022-04-08T08:18:01Z","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"status":"public","ddc":["570"],"type":"journal_article","publication_status":"published","file":[{"file_size":6984654,"file_id":"11138","creator":"dernst","checksum":"1e8672a1e9c3dc0a2d3d0dad89673616","success":1,"relation":"main_file","date_updated":"2022-04-08T08:18:01Z","content_type":"application/pdf","date_created":"2022-04-08T08:18:01Z","file_name":"2019_eLife_Buchwalter.pdf","access_level":"open_access"}],"title":"Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress","fulldoi":"https://doi.org/10.7554/elife.49796","publisher":"eLife Sciences Publications","oa_version":"Published Version","month":"10","external_id":{"pmid":["31599721"]},"_id":"11060","quality_controlled":"1","article_number":"e49796","extern":"1","pmid":1,"intvolume":"         8","publication_identifier":{"issn":["2050-084X"]},"article_type":"original","volume":8,"author":[{"last_name":"Buchwalter","first_name":"Abigail","full_name":"Buchwalter, Abigail"},{"last_name":"Schulte","first_name":"Roberta","full_name":"Schulte, Roberta"},{"full_name":"Tsai, Hsiao","last_name":"Tsai","first_name":"Hsiao"},{"first_name":"Juliana","last_name":"Capitanio","full_name":"Capitanio, Juliana"},{"orcid":"0000-0002-2111-992X","full_name":"HETZER, Martin W","last_name":"HETZER","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","first_name":"Martin W"}],"date_updated":"2024-10-14T12:08:36Z","citation":{"apa":"Buchwalter, A., Schulte, R., Tsai, H., Capitanio, J., &#38; Hetzer, M. (2019). Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.49796\">https://doi.org/10.7554/elife.49796</a>","ista":"Buchwalter A, Schulte R, Tsai H, Capitanio J, Hetzer M. 2019. Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress. eLife. 8, e49796.","ama":"Buchwalter A, Schulte R, Tsai H, Capitanio J, Hetzer M. Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress. <i>eLife</i>. 2019;8. doi:<a href=\"https://doi.org/10.7554/elife.49796\">10.7554/elife.49796</a>","short":"A. Buchwalter, R. Schulte, H. Tsai, J. Capitanio, M. Hetzer, ELife 8 (2019).","ieee":"A. Buchwalter, R. Schulte, H. Tsai, J. Capitanio, and M. Hetzer, “Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress,” <i>eLife</i>, vol. 8. eLife Sciences Publications, 2019.","mla":"Buchwalter, Abigail, et al. “Selective Clearance of the Inner Nuclear Membrane Protein Emerin by Vesicular Transport during ER Stress.” <i>ELife</i>, vol. 8, e49796, eLife Sciences Publications, 2019, doi:<a href=\"https://doi.org/10.7554/elife.49796\">10.7554/elife.49796</a>.","chicago":"Buchwalter, Abigail, Roberta Schulte, Hsiao Tsai, Juliana Capitanio, and Martin Hetzer. “Selective Clearance of the Inner Nuclear Membrane Protein Emerin by Vesicular Transport during ER Stress.” <i>ELife</i>. eLife Sciences Publications, 2019. <a href=\"https://doi.org/10.7554/elife.49796\">https://doi.org/10.7554/elife.49796</a>."},"date_created":"2022-04-07T07:45:02Z","year":"2019","publication":"eLife","abstract":[{"text":"The inner nuclear membrane (INM) is a subdomain of the endoplasmic reticulum (ER) that is gated by the nuclear pore complex. It is unknown whether proteins of the INM and ER are degraded through shared or distinct pathways in mammalian cells. We applied dynamic proteomics to profile protein half-lives and report that INM and ER residents turn over at similar rates, indicating that the INM’s unique topology is not a barrier to turnover. Using a microscopy approach, we observed that the proteasome can degrade INM proteins in situ. However, we also uncovered evidence for selective, vesicular transport-mediated turnover of a single INM protein, emerin, that is potentiated by ER stress. Emerin is rapidly cleared from the INM by a mechanism that requires emerin’s LEM domain to mediate vesicular trafficking to lysosomes. This work demonstrates that the INM can be dynamically remodeled in response to environmental inputs.","lang":"eng"}],"scopus_import":"1","day":"10","date_published":"2019-10-10T00:00:00Z","doi":"10.7554/elife.49796"},{"fulldoi":"https://doi.org/10.1083/jcb.201809123","title":"Visualization of long-lived proteins reveals age mosaicism within nuclei of postmitotic cells","file":[{"creator":"dernst","checksum":"7964ebbf833b0b35f9fba840eea9531d","file_size":2503838,"file_id":"11139","date_created":"2022-04-08T08:26:32Z","content_type":"application/pdf","file_name":"2019_JCB_Toyama.pdf","access_level":"open_access","relation":"main_file","date_updated":"2022-04-08T08:26:32Z","success":1}],"publication_status":"published","ddc":["570"],"type":"journal_article","status":"public","keyword":["Cell Biology"],"license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","page":"433-444","tmp":{"name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","image":"/images/cc_by_nc_sa.png","short":"CC BY-NC-SA (4.0)"},"language":[{"iso":"eng"}],"oa":1,"has_accepted_license":"1","file_date_updated":"2022-04-08T08:26:32Z","article_processing_charge":"No","scopus_import":"1","abstract":[{"text":"Many adult tissues contain postmitotic cells as old as the host organism. The only organelle that does not turn over in these cells is the nucleus, and its maintenance represents a formidable challenge, as it harbors regulatory proteins that persist throughout adulthood. Here we developed strategies to visualize two classes of such long-lived proteins, histones and nucleoporins, to understand the function of protein longevity in nuclear maintenance. Genome-wide mapping of histones revealed specific enrichment of long-lived variants at silent gene loci. Interestingly, nuclear pores are maintained by piecemeal replacement of subunits, resulting in mosaic complexes composed of polypeptides with vastly different ages. In contrast, nondividing quiescent cells remove old nuclear pores in an ESCRT-dependent manner. Our findings reveal distinct molecular strategies of nuclear maintenance, linking lifelong protein persistence to gene regulation and nuclear integrity.","lang":"eng"}],"doi":"10.1083/jcb.201809123","day":"04","date_published":"2019-02-04T00:00:00Z","year":"2019","date_created":"2022-04-07T07:45:11Z","citation":{"chicago":"Toyama, Brandon H., Rafael Arrojo e Drigo, Varda Lev-Ram, Ranjan Ramachandra, Thomas J. Deerinck, Claude Lechene, Mark H. Ellisman, and Martin Hetzer. “Visualization of Long-Lived Proteins Reveals Age Mosaicism within Nuclei of Postmitotic Cells.” <i>Journal of Cell Biology</i>. Rockefeller University Press, 2019. <a href=\"https://doi.org/10.1083/jcb.201809123\">https://doi.org/10.1083/jcb.201809123</a>.","mla":"Toyama, Brandon H., et al. “Visualization of Long-Lived Proteins Reveals Age Mosaicism within Nuclei of Postmitotic Cells.” <i>Journal of Cell Biology</i>, vol. 218, no. 2, Rockefeller University Press, 2019, pp. 433–44, doi:<a href=\"https://doi.org/10.1083/jcb.201809123\">10.1083/jcb.201809123</a>.","short":"B.H. Toyama, R. Arrojo e Drigo, V. Lev-Ram, R. Ramachandra, T.J. Deerinck, C. Lechene, M.H. Ellisman, M. Hetzer, Journal of Cell Biology 218 (2019) 433–444.","ieee":"B. H. Toyama <i>et al.</i>, “Visualization of long-lived proteins reveals age mosaicism within nuclei of postmitotic cells,” <i>Journal of Cell Biology</i>, vol. 218, no. 2. Rockefeller University Press, pp. 433–444, 2019.","ama":"Toyama BH, Arrojo e Drigo R, Lev-Ram V, et al. Visualization of long-lived proteins reveals age mosaicism within nuclei of postmitotic cells. <i>Journal of Cell Biology</i>. 2019;218(2):433-444. doi:<a href=\"https://doi.org/10.1083/jcb.201809123\">10.1083/jcb.201809123</a>","ista":"Toyama BH, Arrojo e Drigo R, Lev-Ram V, Ramachandra R, Deerinck TJ, Lechene C, Ellisman MH, Hetzer M. 2019. Visualization of long-lived proteins reveals age mosaicism within nuclei of postmitotic cells. Journal of Cell Biology. 218(2), 433–444.","apa":"Toyama, B. H., Arrojo e Drigo, R., Lev-Ram, V., Ramachandra, R., Deerinck, T. J., Lechene, C., … Hetzer, M. (2019). Visualization of long-lived proteins reveals age mosaicism within nuclei of postmitotic cells. <i>Journal of Cell Biology</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1083/jcb.201809123\">https://doi.org/10.1083/jcb.201809123</a>"},"publication":"Journal of Cell Biology","author":[{"full_name":"Toyama, Brandon H.","first_name":"Brandon H.","last_name":"Toyama"},{"full_name":"Arrojo e Drigo, Rafael","first_name":"Rafael","last_name":"Arrojo e Drigo"},{"first_name":"Varda","last_name":"Lev-Ram","full_name":"Lev-Ram, Varda"},{"full_name":"Ramachandra, Ranjan","first_name":"Ranjan","last_name":"Ramachandra"},{"full_name":"Deerinck, Thomas J.","first_name":"Thomas J.","last_name":"Deerinck"},{"first_name":"Claude","last_name":"Lechene","full_name":"Lechene, Claude"},{"full_name":"Ellisman, Mark H.","last_name":"Ellisman","first_name":"Mark H."},{"id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","first_name":"Martin W","last_name":"HETZER","full_name":"HETZER, Martin W","orcid":"0000-0002-2111-992X"}],"date_updated":"2024-10-14T11:19:21Z","intvolume":"       218","volume":218,"publication_identifier":{"eissn":["1540-8140"],"issn":["0021-9525"]},"article_type":"original","quality_controlled":"1","extern":"1","pmid":1,"issue":"2","_id":"11061","month":"02","oa_version":"Published Version","publisher":"Rockefeller University Press","external_id":{"pmid":["30552100"]}},{"scopus_import":"1","abstract":[{"text":"Most neurons are not replaced during an animal’s lifetime. This nondividing state is characterized by extreme longevity and age-dependent decline of key regulatory proteins. To study the lifespans of cells and proteins in adult tissues, we combined isotope labeling of mice with a hybrid imaging method (MIMS-EM). Using 15N mapping, we show that liver and pancreas are composed of cells with vastly different ages, many as old as the animal. Strikingly, we also found that a subset of fibroblasts and endothelial cells, both known for their replicative potential, are characterized by the absence of cell division during adulthood. In addition, we show that the primary cilia of beta cells and neurons contains different structural regions with vastly different lifespans. Based on these results, we propose that age mosaicism across multiple scales is a fundamental principle of adult tissue, cell, and protein complex organization.","lang":"eng"}],"day":"06","date_published":"2019-08-06T00:00:00Z","doi":"10.1016/j.cmet.2019.05.010","author":[{"full_name":"Arrojo e Drigo, Rafael","first_name":"Rafael","last_name":"Arrojo e Drigo"},{"first_name":"Varda","last_name":"Lev-Ram","full_name":"Lev-Ram, Varda"},{"full_name":"Tyagi, Swati","first_name":"Swati","last_name":"Tyagi"},{"full_name":"Ramachandra, Ranjan","first_name":"Ranjan","last_name":"Ramachandra"},{"first_name":"Thomas","last_name":"Deerinck","full_name":"Deerinck, Thomas"},{"last_name":"Bushong","first_name":"Eric","full_name":"Bushong, Eric"},{"first_name":"Sebastien","last_name":"Phan","full_name":"Phan, Sebastien"},{"full_name":"Orphan, Victoria","first_name":"Victoria","last_name":"Orphan"},{"full_name":"Lechene, Claude","first_name":"Claude","last_name":"Lechene"},{"full_name":"Ellisman, Mark H.","first_name":"Mark H.","last_name":"Ellisman"},{"full_name":"HETZER, Martin W","orcid":"0000-0002-2111-992X","first_name":"Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","last_name":"HETZER"}],"date_updated":"2025-12-15T10:02:11Z","citation":{"mla":"Arrojo e Drigo, Rafael, et al. “Age Mosaicism across Multiple Scales in Adult Tissues.” <i>Cell Metabolism</i>, vol. 30, no. 2, Elsevier, 2019, p. 343–351.e3, doi:<a href=\"https://doi.org/10.1016/j.cmet.2019.05.010\">10.1016/j.cmet.2019.05.010</a>.","short":"R. Arrojo e Drigo, V. Lev-Ram, S. Tyagi, R. Ramachandra, T. Deerinck, E. Bushong, S. Phan, V. Orphan, C. Lechene, M.H. Ellisman, M. Hetzer, Cell Metabolism 30 (2019) 343–351.e3.","ieee":"R. Arrojo e Drigo <i>et al.</i>, “Age mosaicism across multiple scales in adult tissues,” <i>Cell Metabolism</i>, vol. 30, no. 2. Elsevier, p. 343–351.e3, 2019.","chicago":"Arrojo e Drigo, Rafael, Varda Lev-Ram, Swati Tyagi, Ranjan Ramachandra, Thomas Deerinck, Eric Bushong, Sebastien Phan, et al. “Age Mosaicism across Multiple Scales in Adult Tissues.” <i>Cell Metabolism</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.cmet.2019.05.010\">https://doi.org/10.1016/j.cmet.2019.05.010</a>.","apa":"Arrojo e Drigo, R., Lev-Ram, V., Tyagi, S., Ramachandra, R., Deerinck, T., Bushong, E., … Hetzer, M. (2019). Age mosaicism across multiple scales in adult tissues. <i>Cell Metabolism</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cmet.2019.05.010\">https://doi.org/10.1016/j.cmet.2019.05.010</a>","ista":"Arrojo e Drigo R, Lev-Ram V, Tyagi S, Ramachandra R, Deerinck T, Bushong E, Phan S, Orphan V, Lechene C, Ellisman MH, Hetzer M. 2019. Age mosaicism across multiple scales in adult tissues. Cell Metabolism. 30(2), 343–351.e3.","ama":"Arrojo e Drigo R, Lev-Ram V, Tyagi S, et al. Age mosaicism across multiple scales in adult tissues. <i>Cell Metabolism</i>. 2019;30(2):343-351.e3. doi:<a href=\"https://doi.org/10.1016/j.cmet.2019.05.010\">10.1016/j.cmet.2019.05.010</a>"},"date_created":"2022-04-07T07:45:21Z","year":"2019","publication":"Cell Metabolism","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.cmet.2019.05.010"}],"quality_controlled":"1","issue":"2","extern":"1","pmid":1,"intvolume":"        30","publication_identifier":{"issn":["1550-4131"]},"article_type":"original","volume":30,"publisher":"Elsevier","month":"08","oa_version":"Published Version","external_id":{"pmid":["31178361"]},"department":[{"_id":"MaHe"}],"_id":"11062","publication_status":"published","title":"Age mosaicism across multiple scales in adult tissues","fulldoi":"https://doi.org/10.1016/j.cmet.2019.05.010","status":"public","type":"journal_article","keyword":["Cell Biology","Molecular Biology","Physiology"],"oa":1,"article_processing_charge":"No","language":[{"iso":"eng"}],"page":"343-351.e3","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"publisher":"Dryad","related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"11060"}]},"oa_version":"Published Version","oa":1,"month":"10","article_processing_charge":"No","tmp":{"short":"CC0 (1.0)","name":"Creative Commons Public Domain Dedication (CC0 1.0)","image":"/images/cc_0.png","legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"13079","license":"https://creativecommons.org/publicdomain/zero/1.0/","extern":"1","author":[{"full_name":"Buchwalter, Abigail","last_name":"Buchwalter","first_name":"Abigail"},{"first_name":"Roberta","last_name":"Schulte","full_name":"Schulte, Roberta"},{"first_name":"Hsiao","last_name":"Tsai","full_name":"Tsai, Hsiao"},{"last_name":"Capitanio","first_name":"Juliana","full_name":"Capitanio, Juliana"},{"last_name":"HETZER","first_name":"Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","orcid":"0000-0002-2111-992X","full_name":"HETZER, Martin W"}],"status":"public","date_updated":"2024-10-14T12:08:37Z","citation":{"short":"A. Buchwalter, R. Schulte, H. Tsai, J. Capitanio, M. Hetzer, (2019).","ieee":"A. Buchwalter, R. Schulte, H. Tsai, J. Capitanio, and M. Hetzer, “Data from: Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress.” Dryad, 2019.","mla":"Buchwalter, Abigail, et al. <i>Data from: Selective Clearance of the Inner Nuclear Membrane Protein Emerin by Vesicular Transport during ER Stress</i>. Dryad, 2019, doi:<a href=\"https://doi.org/10.5061/DRYAD.N0R525H\">10.5061/DRYAD.N0R525H</a>.","chicago":"Buchwalter, Abigail, Roberta Schulte, Hsiao Tsai, Juliana Capitanio, and Martin Hetzer. “Data from: Selective Clearance of the Inner Nuclear Membrane Protein Emerin by Vesicular Transport during ER Stress.” Dryad, 2019. <a href=\"https://doi.org/10.5061/DRYAD.N0R525H\">https://doi.org/10.5061/DRYAD.N0R525H</a>.","apa":"Buchwalter, A., Schulte, R., Tsai, H., Capitanio, J., &#38; Hetzer, M. (2019). Data from: Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress. Dryad. <a href=\"https://doi.org/10.5061/DRYAD.N0R525H\">https://doi.org/10.5061/DRYAD.N0R525H</a>","ama":"Buchwalter A, Schulte R, Tsai H, Capitanio J, Hetzer M. Data from: Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress. 2019. doi:<a href=\"https://doi.org/10.5061/DRYAD.N0R525H\">10.5061/DRYAD.N0R525H</a>","ista":"Buchwalter A, Schulte R, Tsai H, Capitanio J, Hetzer M. 2019. Data from: Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress, Dryad, <a href=\"https://doi.org/10.5061/DRYAD.N0R525H\">10.5061/DRYAD.N0R525H</a>."},"date_created":"2023-05-23T17:09:30Z","year":"2019","ddc":["570"],"type":"research_data_reference","main_file_link":[{"url":"https://doi.org/10.5061/dryad.n0r525h","open_access":"1"}],"abstract":[{"lang":"eng","text":"The inner nuclear membrane (INM) is a subdomain of the endoplasmic reticulum (ER) that is gated by the nuclear pore complex. It is unknown whether proteins of the INM and ER are degraded through shared or distinct pathways in mammalian cells. We applied dynamic proteomics to profile protein half-lives and report that INM and ER residents turn over at similar rates, indicating that the INM’s unique topology is not a barrier to turnover. Using a microscopy approach, we observed that the proteasome can degrade INM proteins in situ. However, we also uncovered evidence for selective, vesicular transport-mediated turnover of a single INM protein, emerin, that is potentiated by ER stress. Emerin is rapidly cleared from the INM by a mechanism that requires emerin’s LEM domain to mediate vesicular trafficking to lysosomes. This work demonstrates that the INM can be dynamically remodeled in response to environmental inputs."}],"title":"Data from: Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress","day":"28","date_published":"2019-10-28T00:00:00Z","doi":"10.5061/DRYAD.N0R525H","fulldoi":"https://doi.org/10.5061/DRYAD.N0R525H"}]