美国加州大学Nicole G. Coufal和Christopher K. Glass研究组发现，人类小胶质细胞的成熟是由特定的基因调控网络支撑的。2023年8月14日，国际知名学术期刊《免疫》发表了这一成果。

他们描述了胎儿和出生后人类小胶质细胞的阶段特异性转录组和表观遗传景观，并在诱导多能干细胞(iPSC)来源的小胶质细胞、脑类器官和植入人源化小鼠后获得了相应的数据。考虑转录因子(TF)共发生和增强子活性的计算方法的并行发展，允许预测与胎儿和出生后小胶质细胞相关的共享和状态特异性基因调控网络。

此外，在将iPSC细胞植入人源化小鼠后，人类胎儿到产后过渡的许多特征以一种时间依赖性的方式重现。这些数据和伴随的计算方法将有助于，进一步阐明人类小胶质细胞获得阶段和疾病特异性表型的机制。

据了解，小胶质细胞的表型受到大脑环境的高度调节，但人们对指定人类小胶质细胞成熟的转录网络知之甚少。

附：英文原文

Title: Human microglia maturation is underpinned by specific gene regulatory networks

Author: Claudia Z. Han, Rick Z. Li, Emily Hansen, Samantha Trescott, Bethany R. Fixsen, Celina T. Nguyen, Cristina M. Mora, Nathanael J. Spann, Hunter R. Bennett, Olivier Poirion, Justin Buchanan, Anna S. Warden, Bing Xia, Johannes C.M. Schlachetzki, Martina P. Pasillas, Sebastian Preissl, Allen Wang, Carolyn O’Connor, Shreya Shriram, Roy Kim, Danielle Schafer, Gabriela Ramirez, Jean Challacombe, Samuel A. Anavim, Avalon Johnson, Mihir Gupta, Ian A. Glass, Michael L. Levy, Sharona Ben Haim, David D. Gonda, Louise Laurent, Jennifer F. Hughes, David C. Page, Mathew Blurton-Jones, Christopher K. Glass, Nicole G. Coufal

Issue&Volume: 2023-08-14

Abstract: 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.

DOI: 10.1016/j.immuni.2023.07.016

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00329-1