{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T15:18:00Z","timestamp":1771600680027,"version":"3.50.1"},"posted":{"date-parts":[[2026,2,20]]},"group-title":"In Review","reference-count":0,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,12]]},"abstract":"<title>Abstract<\/title>\n                <p>Early immune perturbations increase the risk of brain disorders, yet the mechanisms underlying the functional maturation of microglia, the brain resident immune cells, remain poorly defined. Here, we used mathematical modeling of hippocampus and cerebellum to reconstruct postnatal microglial development. We identified a proliferative-to-quiescent (P\/Q) switch around P3\/P4 that preceded the acquisition of morphological complexity and efficient phagocytosis and was accompanied by changes in cell-cycle dynamics and metabolic state. This P\/Q switch was recapitulated in repopulation contexts in mice and in the fetal human brain. Pharmacological and genetic perturbations of proliferation impaired subsequent morphological complexity and phagocytosis efficiency. Finally, microglial developmental maturation was associated with chromatin remodeling and driven by the epigenetic regulator Ikaros. These findings uncover the milestones of microglial development, revealing a potential period of early vulnerability and establishing an unexpected linkage between proliferation and phagocytosis essential to understanding how these processes are coordinated in neurodegenerative disorders.<\/p>","DOI":"10.21203\/rs.3.rs-8344753\/v1","type":"posted-content","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T14:42:26Z","timestamp":1771598546000},"source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic control of microglial developmental milestones from proliferative progenitors to efficient phagocytes"],"prefix":"10.21203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8415-096X","authenticated-orcid":false,"given":"Amanda","family":"Sierra","sequence":"first","affiliation":[{"name":"Achucarro Basque Center for Neuroscience"}]},{"given":"Marta","family":"Pereira-Iglesias","sequence":"additional","affiliation":[{"name":"Achucarro Basque Center for Neuroscience"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3590-606X","authenticated-orcid":false,"given":"William","family":"Martinson","sequence":"additional","affiliation":[{"name":"Crick Institute"}]},{"given":"Carles","family":"Falco","sequence":"additional","affiliation":[{"name":"Oxford University"}]},{"given":"Joel","family":"Maldonado-Teixido","sequence":"additional","affiliation":[{"name":"Achucarro Basque Center for Neuroscience"}]},{"given":"Marco","family":"Gonzalez-Dominguez","sequence":"additional","affiliation":[{"name":"Achucarro Basque Center for Neuroscience"}]},{"given":"Rodrigo","family":"Senovilla-Ganzo","sequence":"additional","affiliation":[{"name":"College de France"}]},{"given":"Eva","family":"Benito","sequence":"additional","affiliation":[{"name":"Achucarro Basque Center for Neuroscience"}]},{"given":"Soledad","family":"Beccari","sequence":"additional","affiliation":[{"name":"Achucarro Basque Center for Neuroscience"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6072-3313","authenticated-orcid":false,"given":"Jorge","family":"Valero","sequence":"additional","affiliation":[{"name":"University of Salamanca"}]},{"given":"Bella","family":"Mora","sequence":"additional","affiliation":[{"name":"IBIS"}]},{"given":"Ivan","family":"Ballasch","sequence":"additional","affiliation":[{"name":"University of Barcelona"}]},{"given":"Sarah","family":"Viguier","sequence":"additional","affiliation":[{"name":"college de France"}]},{"given":"Philipp","family":"Haene","sequence":"additional","affiliation":[{"name":"Zurich University"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0244-0938","authenticated-orcid":false,"given":"Molly","family":"Boettiger","sequence":"additional","affiliation":[{"name":"University of Colorado"}]},{"given":"Julie","family":"Haines","sequence":"additional","affiliation":[]},{"given":"Alba","family":"El\u00edas-Tersa","sequence":"additional","affiliation":[{"name":"University of Barcelona"}]},{"given":"Yasmina","family":"Manso","sequence":"additional","affiliation":[{"name":"University of Barcelona"}]},{"given":"Laura","family":"Parkkinen","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, the Oxford Brain Bank, University of Oxford"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8271-612X","authenticated-orcid":false,"given":"Ana","family":"Aransay","sequence":"additional","affiliation":[{"name":"CIC Biogune"}]},{"given":"Federico","family":"Soria","sequence":"additional","affiliation":[{"name":"Achucarro Basque Center for Neuroscience"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2258-6490","authenticated-orcid":false,"given":"Angelo","family":"D'Alessandro","sequence":"additional","affiliation":[{"name":"University of Colorado Anschutz Medical Campus"}]},{"given":"Eduardo","family":"Soriano","sequence":"additional","affiliation":[{"name":"University of Barcelona"}]},{"given":"Morgane","family":"Thion","sequence":"additional","affiliation":[{"name":"College de France"}]},{"given":"Sonia","family":"Garel","sequence":"additional","affiliation":[{"name":"\u00c9cole Normale Sup\u00e9rieure - PSL"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7220-5369","authenticated-orcid":false,"given":"Melanie","family":"Greter","sequence":"additional","affiliation":[{"name":"University of Zurich"}]},{"given":"Albert","family":"Giralt","sequence":"additional","affiliation":[{"name":"University of Barcelona"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5459-6207","authenticated-orcid":false,"given":"Alberto","family":"Pascual","sequence":"additional","affiliation":[{"name":"hospital universitario virgen del rocio\/CSIC\/Universidad de Sevilla"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9048-4237","authenticated-orcid":false,"given":"Fernando","family":"Garcia-Moreno","sequence":"additional","affiliation":[{"name":"Achucarro"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5984-8407","authenticated-orcid":false,"given":"David","family":"Menassa","sequence":"additional","affiliation":[{"name":"Oxford University"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8819-4660","authenticated-orcid":false,"given":"Jose","family":"Carrillo","sequence":"additional","affiliation":[{"name":"Oxford University"}]}],"member":"297","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/www.researchsquare.com\/article\/rs-8344753\/v1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.researchsquare.com\/article\/rs-8344753\/v1.html","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T14:42:26Z","timestamp":1771598546000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchsquare.com\/article\/rs-8344753\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,20]]},"references-count":0,"URL":"https:\/\/doi.org\/10.21203\/rs.3.rs-8344753\/v1","relation":{},"subject":[],"published":{"date-parts":[[2026,2,20]]},"subtype":"preprint"}}