Human microglia maturation is underpinned by specific gene regulatory networks
Summary
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. Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
| Authors | Han CZ, Li RZ, Hansen E, Trescott S, Fixsen BR, Nguyen CT, Mora CM, Spann NJ, Bennett HR, Poirion O, Buchanan J, Warden AS, Xia B, Schlachetzki JCM, Pasillas MP, Preissl S, Wang A, O'Connor C, Shriram S, Kim R, Schafer D, Ramirez G, Challacombe J, Anavim SA, Johnson A, Gupta M, Glass IA, Birth Defects Research Laboratory, Levy ML, Haim SB, Gonda DD, Laurent L, Hughes JF, Page DC, Blurton-Jones M, Glass CK, Coufal NG |
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| Journal | Immunity |
| Publication Date | 2023 Sep 12;56(9):2152-2171.e13 |
| PubMed | 37582369 |
| PubMed Central | PMC10529991 |
| DOI | 10.1016/j.immuni.2023.07.016 |