作者
Claudia Z. Han,Rick Z. Li,Emily Hansen,Samantha Trescott,Bethany Fixsen,Celina Nguyen,Cristina Mora,Nathanael J. Spann,Hunter Bennett,Olivier Poirion,Justin Buchanan,Anna S. Warden,Bing Xia,J Schlachetzki,Martina P. Pasillas,Sebastian Preißl,Allen Wang,Carolyn O’Connor,Shreya Shriram,Roy Kim,Danielle Schafer,Gabriela Ramírez,Jean F. Challacombe,Samuel A. Anavim,Avalon Johnson,Mihir Gupta,Ian A. Glass,Michael L. Levy,S Haim,David Gonda,Louise C. Laurent,Jennifer F. Hughes,David C. Page,Mathew Blurton‐Jones,Christopher K. Glass,Nicole Coufal
摘要
Microglia phenotypes are highly regulated by the brain environment, but the transcriptional networks that specify the maturation of human microglia are poorly understood. Here, we characterized stage-specific transcriptomes and epigenetic landscapes of fetal and postnatal human microglia and acquired corresponding data in induced pluripotent stem cell (iPSC)-derived microglia, in cerebral organoids, and following engraftment into humanized mice. Parallel development of computational approaches that considered transcription factor (TF) co-occurrence and enhancer activity allowed prediction of shared and state-specific gene regulatory networks associated with fetal and postnatal microglia. Additionally, many features of the human fetal-to-postnatal transition were recapitulated in a time-dependent manner following the engraftment of iPSC cells into humanized mice. These data and accompanying computational approaches will facilitate further efforts to elucidate mechanisms by which human microglia acquire stage- and disease-specific phenotypes.