{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T13:52:19Z","timestamp":1772545939613,"version":"3.50.1"},"reference-count":28,"publisher":"Proceedings of the National Academy of Sciences","issue":"18","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,5,6]]},"abstract":"<jats:p>ATP-dependent chromatin remodeling complexes are a notable group of epigenetic modifiers that use the energy of ATP hydrolysis to change the structure of chromatin, thereby altering its accessibility to nuclear factors. BAF250a (ARID1a) is a unique and defining subunit of the BAF chromatin remodeling complex with the potential to facilitate chromosome alterations critical during development. Our studies show that ablation of BAF250a in early mouse embryos results in developmental arrest (about embryonic day 6.5) and absence of the mesodermal layer, indicating its critical role in early germ-layer formation. Moreover, BAF250a deficiency compromises ES cell pluripotency, severely inhibits self-renewal, and promotes differentiation into primitive endoderm-like cells under normal feeder-free culture conditions. Interestingly, this phenotype can be partially rescued by the presence of embryonic fibroblast cells. DNA microarray, immunostaining, and RNA analyses revealed that BAF250a-mediated chromatin remodeling contributes to the proper expression of numerous genes involved in ES cell self-renewal, including Sox2, Utf1, and Oct4. Furthermore, the pluripotency defects in BAF250a mutant ES cells appear to be cell lineage-specific. For example, embryoid body-based analyses demonstrated that BAF250a-ablated stem cells are defective in differentiating into fully functional mesoderm-derived cardiomyocytes and adipocytes but are capable of differentiating into ectoderm-derived neurons. Our results suggest that BAF250a is a key component of the gene regulatory machinery in ES cells controlling self-renewal, differentiation, and cell lineage decisions.<\/jats:p>","DOI":"10.1073\/pnas.0801802105","type":"journal-article","created":{"date-parts":[[2008,5,1]],"date-time":"2008-05-01T01:24:51Z","timestamp":1209605091000},"page":"6656-6661","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":293,"title":["ES cell pluripotency and germ-layer formation require the SWI\/SNF chromatin remodeling component BAF250a"],"prefix":"10.1073","volume":"105","author":[{"given":"Xiaolin","family":"Gao","sequence":"first","affiliation":[{"name":"*Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Richard Simches Research Center, 185 Cambridge Street, Boston, MA 02114;"}]},{"given":"Peri","family":"Tate","sequence":"additional","affiliation":[{"name":"Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, United Kingdom; and"}]},{"given":"Ping","family":"Hu","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Molecular and Cell Biology, and"}]},{"given":"Robert","family":"Tjian","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Molecular and Cell Biology, and"},{"name":"Li Ka Shing Center for Biomedical and Health Sciences, University of California, Berkeley, CA 94720"}]},{"given":"William C.","family":"Skarnes","sequence":"additional","affiliation":[{"name":"Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, United Kingdom; and"}]},{"given":"Zhong","family":"Wang","sequence":"additional","affiliation":[{"name":"*Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Richard Simches Research Center, 185 Cambridge Street, Boston, MA 02114;"}]}],"member":"341","published-online":{"date-parts":[[2008,5,6]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.02.010"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1882"},{"key":"e_1_3_3_3_2","first-page":"143","article-title":"The SWI\/SNF family of ATP-dependent chromatin remodelers: similar mechanisms for diverse functions","volume":"274","author":"Wang W","year":"2003","unstructured":"W Wang, The SWI\/SNF family of ATP-dependent chromatin remodelers: similar mechanisms for diverse functions. 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