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Microglia has been recognized as key regulators of neural stem\/progenitor cells (NSPCs) and brain functions. Chromatin accessibility is implicated in immune cell development and functional regulation. However, it is still unknown whether and how chromatin remodelling regulates the phenotypic plasticity of microglia and exerts what kind of effects on NSPCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the role of chromatin accessibility in microglia by deleting chromatin remodelling gene <jats:italic>Arid1a<\/jats:italic> using microglia\u2010specific Cx3cr1\u2010cre and Cx3cr1\u2010CreERT2 mice. RNA\u2010seq and ATAC\u2010seq were performed to dissect the molecular mechanisms. In addition, we examined postnatal M1\/M2 microglia polarization and analysed neuronal differentiation of NSPCs. Finally, we tested the effects of microglial <jats:italic>Arid1a<\/jats:italic> deletion on mouse behaviours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Increased chromatin accessibility upon <jats:italic>Arid1a<\/jats:italic> ablation resulted in enhanced M1 microglial polarization and weakened M2 polarization, which led to abnormal neurogenesis and anxiety\u2010like behaviours. Switching the polarization state under IL4 stimulation could rescue abnormal neurogenesis, supporting an essential role for chromatin remodeler ARID1A in balancing microglial polarization and brain functions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study identifies ARID1A\u00a0as a central regulator of microglia polarization, establishing a mechanistic link between chromatin remodelling, neurogenesis and mouse behaviours, and highlights the potential development of innovative therapeutics exploiting the innate regenerative capacity of the nervous system.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cpr.13314","type":"journal-article","created":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T05:34:24Z","timestamp":1658295264000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Abnormal microglial polarization induced by <scp><i>Arid1a<\/i><\/scp> deletion leads to neuronal differentiation deficits"],"prefix":"10.1111","volume":"55","author":[{"given":"Maolei","family":"Gong","sequence":"first","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology Chinese Academy of Sciences  Beijing China"},{"name":"Institute for Stem Cell and Regeneration Chinese Academy of Sciences  Beijing China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoxi","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology Chinese Academy of Sciences  Beijing China"},{"name":"Institute for Stem Cell and Regeneration Chinese Academy of Sciences  Beijing China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine  Beijing China"},{"name":"Savaid Medical School University of Chinese Academy of Sciences  Beijing 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