生物
过渡(遗传学)
大脑发育
小胶质细胞
神经科学
转录组
免疫系统
发病机制
基因
人脑
中枢神经系统
免疫学
遗传学
基因表达
炎症
作者
Yanxin Li,Zhongqiu Li,Min Yang,Feiyang Wang,Yuehong Zhang,Rong Li,Qian Li,Yi Gong,Binhong Wang,Baoguang Fan,Chunyue Wang,Lei Chen,Hong Li,Jennie Ong,Zhao‐Qian Teng,Lei Jin,Yanling Wang,Peng Du,Jianwei Jiao
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2022-04-01
卷期号:29 (4): 620-634.e6
被引量:26
标识
DOI:10.1016/j.stem.2022.02.004
摘要
Region-related heterogeneity and state transitions of microglia are important for brain development and neurological pathogenesis. However, regional specialization and state transition in microglia during early human CNS development remain unclear. Here, we profile single-cell transcriptomes of microglia from distinct regions of the developing human brain, and combined with experimental verification, we define and characterize early microglial fate determinations related to regional specification and state transition. We identified several subclasses of neuronal gene-enriched microglia with regional specification that dynamically and transiently appeared as early brain regions formed. In contrast, immune-related microglia were regionally specialized at later stages of CNS development. Surprisingly, we discovered that region-specialized immune-related microglia exit from a relative resting state and transition into distinct active states. In addition, we experimentally verified the microglial state transition. Finally, we showed that the state transition is conserved but that there are molecular differences in developing microglia in humans and mice.
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