A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment
A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment
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DOI：
10.1038/s41593-019-0393-4
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发表时间：
2019-06-01
影响因子：
25
通讯作者：
Movahedi, Kiavash
中科院分区：
文献类型：
--
作者：
Van Hove, Hannah;Martens, Liesbet;Movahedi, Kiavash
虽然实质小胶质细胞在脑内环境稳定和疾病中的作用相当清楚，但其他脑内驻留的髓样细胞仍然不太清楚。通过解剖边界区域并将单细胞RNA测序与高维细胞计数、批量RNA测序、命运作图和显微镜相结合，我们揭示了非实质脑巨噬细胞的多样性。存在于硬脑膜、硬膜下脑膜和脉络丛中的边界相关巨噬细胞（BAM）由具有组织特异性转录特征的不同亚群组成，其细胞组成在出生后发育过程中发生变化。BAM表现出混合的个体发育，和子集显示出不同的自我更新能力后耗尽和再增殖。单细胞和命运映射分析都表明，有一个独特的小胶质细胞亚群居住在脉络丛上皮的顶面。最后，基因网络分析和条件删除揭示了IRF 8作为驱动脑巨噬细胞成熟和多样性的主调节因子。我们的研究结果为理解健康和患病大脑中宿主-巨噬细胞相互作用提供了一个框架。
While the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less well understood. By dissecting border regions and combining single-cell RNA-sequencing with high-dimensional cytometry, bulk RNA-sequencing, fate-mapping and microscopy, we reveal the diversity of non-parenchymal brain macrophages. Border-associated macrophages (BAMs) residing in the dura mater, subdural meninges and choroid plexus consisted of distinct subsets with tissue-specific transcriptional signatures, and their cellular composition changed during postnatal development. BAMs exhibited a mixed ontogeny, and subsets displayed distinct self-renewal capacity following depletion and repopulation. Single-cell and fate-mapping analysis both suggested that there is a unique microglial subset residing on the apical surface of the choroid plexus epithelium. Finally, gene network analysis and conditional deletion revealed IRF8 as a master regulator that drives the maturation and diversity of brain macrophages. Our results provide a framework for understanding host-macrophage interactions in both the healthy and diseased brain.