Subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave.
Subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave.
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DOI：
10.7554/elife.66738
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发表时间：
2021-08-23
期刊：
影响因子：
7.7
通讯作者：
Green KN
中科院分区：
文献类型：
--
作者：
Hohsfield LA;Najafi AR;Ghorbanian Y;Soni N;Crapser J;Figueroa Velez DX;Jiang S;Royer SE;Kim SJ;Henningfield CM;Anderson A;Gandhi SP;Mortazavi A;Inlay MA;Green KN
小胶质细胞是大脑中的骨髓细胞，在大脑防御、体内平衡和疾病中起着核心作用。使用长期的集落刺激因子1受体抑制剂（CSF1Ri）的方法，我们报告了一个前所未有的水平的小胶质细胞耗竭，并建立了一个模型系统，实现了一个空的小胶质细胞龛在成人大脑。我们发现一个髓样细胞从脑室下区和相关的白色区迁移。在CSF1Ri之后，这些变形虫细胞在动态波中径向和切向地迁移，以不同的模式填充大脑，以取代小胶质细胞耗尽的大脑。这些再生细胞富含疾病相关的小胶质细胞基因，并表现出与白质相关的小胶质细胞相似的表型和转录谱。我们的研究结果揭示了中枢神经系统髓样细胞的重叠和独特的功能复杂性和多样性，并为小鼠大脑中小胶质细胞功能和动力学的重建提供了新的见解。
Microglia, the brain’s resident myeloid cells, play central roles in brain defense, homeostasis, and disease. Using a prolonged colony-stimulating factor 1 receptor inhibitor (CSF1Ri) approach, we report an unprecedented level of microglial depletion and establish a model system that achieves an empty microglial niche in the adult brain. We identify a myeloid cell that migrates from the subventricular zone and associated white matter areas. Following CSF1Ri, these amoeboid cells migrate radially and tangentially in a dynamic wave filling the brain in a distinct pattern, to replace the microglial-depleted brain. These repopulating cells are enriched in disease-associated microglia genes and exhibit similar phenotypic and transcriptional profiles to white-matter-associated microglia. Our findings shed light on the overlapping and distinct functional complexity and diversity of myeloid cells of the CNS and provide new insight into repopulating microglia function and dynamics in the mouse brain.