脑环境高度调节了微胶质细胞表型，但尚不清楚规范人类微胶质细胞成熟的转录网络。本研究对胎儿和出生后的人类微胶质细胞特定发育时期的转录组和表观遗传景观进行了表征，并在诱导多能干细胞（iPSC）衍生的微胶质细胞、脑器官样体和移植到人性化小鼠体内后获得相应的数据。采用考虑转录因子（TF）共存和增强子活性的计算方法平行开发，可预测与胎儿和出生后微胶质细胞相关的共享和状态特异性的基因调控网络。此外，通过将iPSC细胞移植到人性化小鼠体内，许多人类胎儿到出生后的转变特征也得以依时间演变的方式再现。这些数据和伴随的计算方法将有助于进一步阐明人类微胶质细胞获得特定发育阶段和疾病特异性表型的机制。版权 © 2023 The Authors. Elsevier Inc.。保留所有权利。

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.