Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation
Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation
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DOI：
10.1126/science.aat7554
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发表时间：
2019-01-25
期刊：
影响因子：
56.9
通讯作者：
Prinz, Marco
中科院分区：
文献类型：
--
作者：
Costa Jordao, Marta Joana;Sankowski, Roman;Prinz, Marco
先天性免疫细胞区室在健康中枢神经系统（CNS）中高度多样，包括实质和非实质巨噬细胞。然而，这种复杂性在炎症环境中通过募集循环骨髓细胞而增加。目前还不清楚哪些疾病特异性骨髓亚群存在，以及它们在CNS病理过程中的转录谱和动力学是什么。结合深入的单细胞转录组分析，命运定位，体内成像，克隆分析和转基因小鼠品系，我们全面表征了神经炎症过程中几个CNS隔室中未被重视的骨髓亚群。在炎症过程中，CNS巨噬细胞亚群进行自我更新，随机增殖转向克隆扩张。最后，功能研究表明，内源性CNS组织巨噬细胞对于抗原呈递是多余的。我们的研究结果突出了骨髓细胞的多样性，并提供了对大脑先天免疫系统的见解。
The innate immune cell compartment is highly diverse in the healthy central nervous system (CNS), including parenchymal and non-parenchymal macrophages. However, this complexity is increased in inflammatory settings by the recruitment of circulating myeloid cells. It is unclear which disease-specific myeloid subsets exist and what their transcriptional profiles and dynamics during CNS pathology are. Combining deep single-cell transcriptome analysis, fate mapping, in vivo imaging, clonal analysis, and transgenic mouse lines, we comprehensively characterized unappreciated myeloid subsets in several CNS compartments during neuroinflammation. During inflammation, CNS macrophage subsets undergo self-renewal, and random proliferation shifts toward clonal expansion. Last, functional studies demonstrated that endogenous CNS tissue macrophages are redundant for antigen presentation. Our results highlight myeloid cell diversity and provide insights into the brain's innate immune system.