Mapping microglia states in the human brain through the integration of high-dimensional techniques
Mapping microglia states in the human brain through the integration of high-dimensional techniques
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DOI：
10.1038/s41593-019-0532-y
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发表时间：
2019-12-01
影响因子：
25
通讯作者：
Prinz, Marco
中科院分区：
文献类型：
--
作者：
Sankowski, Roman;Bottcher, Chotima;Prinz, Marco
小胶质细胞是CNS的组织驻留巨噬细胞，其协调局部免疫应答并促成若干神经和精神疾病。关于人类小胶质细胞以及它们如何在病理过程中协调其高度可塑性，特定于环境的适应性反应知之甚少。在这里，我们结合了两种高维技术，单细胞RNA测序和飞行时间质谱仪，以确定人类大脑中的小胶质细胞在稳态和疾病期间的状态。这种方法使我们能够识别和表征人类小胶质细胞中以前不受重视的转录状态谱。这些转录状态由它们的空间分布决定，并且它们随着衰老和脑肿瘤病理学而进一步改变。这种对人类中枢神经系统中多种小胶质细胞表型的描述可能为亚群特异性治疗干预开辟有希望的新途径。
Microglia are tissue-resident macrophages of the CNS that orchestrate local immune responses and contribute to several neurological and psychiatric diseases. Little is known about human microglia and how they orchestrate their highly plastic, context-specific adaptive responses during pathology. Here we combined two high-dimensional technologies, single-cell RNA-sequencing and time-of-flight mass cytometry, to identify microglia states in the human brain during homeostasis and disease. This approach enabled us to identify and characterize a previously unappreciated spectrum of transcriptional states in human microglia. These transcriptional states are determined by their spatial distribution, and they further change with aging and brain tumor pathology. This description of multiple microglia phenotypes in the human CNS may open promising new avenues for subset-specific therapeutic interventions.