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We developed an in vivo gain-of-function Perturb-seq platform, termed iGOF\u2013Perturb-seq, to build a functional atlas of ~1000 transcription factors (TFs) in astrocytes, a cell type essential to many brain functions. We then identified cofunctional modules, annotated uncharacterized TFs, and predicted disease-associated TF clusters. Furthermore, iGOF\u2013Perturb-seq performed in a mouse neuroinflammatory model identified\n                    <jats:italic toggle=\"yes\">Ferd3l<\/jats:italic>\n                    as a therapeutic candidate, and astrocyte-specific overexpression of\n                    <jats:italic toggle=\"yes\">Ferd3l<\/jats:italic>\n                    alleviated Alzheimer\u2019s disease symptoms in mice. This study provides resources for understanding gene regulation and disease mechanisms in vivo and for identifying potential therapeutic targets for different brain diseases.\n                  <\/jats:p>","DOI":"10.1126\/science.adw2156","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T17:59:47Z","timestamp":1776967187000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Mapping transcription factor functions in astrocytes using in vivo gain-of-function Perturb-seq"],"prefix":"10.1126","volume":"392","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6444-6421","authenticated-orcid":true,"given":"Liansheng","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 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