论文题目：Decoding the Temporal and Regional Specification of Microglia in the Developing Human Brain

作者：Li Y, Li Z, Yang M, Wang F, Zhang Y, Li R, Li Q, Gong Y, Wang B, Fan B, Wang C, Chen L, Li H, Ong J, Teng Z, Jin L, Wang YL, Du P, Jiao J

日期：2022.4

发表期刊：Cell Stem Cell

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. 

关键词：activated state; central nervous system; developing human brain; heterogeneity; microglia; regional specification; single-cell sequencing