文章基本信息

标题：Neural progenitor cells mediated by H2A.Z.2 regulate microglial development via Cxcl14 in the embryonic brain
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作者：Zhongqiu Li ; Yanxin Li ; Jianwei Jiao 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2019
卷号：116
期号：48
页码：24122-24132
DOI：10.1073/pnas.1913978116
出版社：The National Academy of Sciences of the United States of America
摘要：Microglia, the resident immune cells of the central nervous system, play an important role in the brain. Microglia have a special spatiotemporal distribution during the development of the cerebral cortex. Neural progenitor cells (NPCs) are the main source of neural-specific cells in the early brain. It is unclear whether NPCs affect microglial development and what molecular mechanisms control early microglial localization. H2A.Z.2, a histone variant of H2A, has a key role in gene expression regulation, genomic stability, and chromatin remodeling, but its function in brain development is not fully understood. Here, we found that the specific deletion of H2A.Z.2 in neural progenitor cells led to an abnormal increase in microglia in the ventricular zone/subventricular zone (VZ/SVZ) of the embryonic cortex. Mechanistically, H2A.Z.2 regulated microglial development by incorporating G9a into the promoter region of Cxcl14 and promoted H3k9me2 modification to inhibit the transcription of Cxcl14 in neural progenitor cells. Meanwhile, we found that the deletion of H2A.Z.2 in microglia itself had no significant effect on microglial development in the early cerebral cortex. Our findings demonstrate a key role of H2A.Z.2 in neural progenitor cells in controlling microglial development and broaden our knowledge of 2 different types of cells that may affect each other through crosstalk in the central nervous system..
关键词：H2A.Z.2 ; neural progenitor cells ; microglial development ; Cxcl14 ; G9a