Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution
Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution
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DOI：
10.1038/s41586-019-0924-x
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发表时间：
2019-02-21
期刊：
影响因子：
64.8
通讯作者：
Prinz, Marco
中科院分区：
文献类型：
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作者：
Masuda, Takahiro;Sankowski, Roman;Prinz, Marco
小胶质细胞不仅在神经发育和内环境稳定中发挥关键作用，而且在中枢神经系统的神经退行性疾病和神经炎症性疾病中也发挥关键作用(1-4)。这些高度多样化和专门化的功能可能是由已经存在的原位小胶质细胞亚群执行的，也可能是由根据需要从同质细胞池发展而来的特定小胶质细胞亚群执行的。然而，关于在发育或疾病期间中枢神经系统中是否存在空间和时间受限的小胶质细胞亚类，人们知之甚少。在这里，我们结合大规模平行单细胞分析、单分子荧光原位杂交、先进的免疫组织化学和计算模型来全面表征中枢神经系统发育和疾病过程中多个区域的小胶质细胞亚类。对小鼠中枢神经系统内稳态期间组织的单细胞分析揭示了特定的时间和区域依赖的小胶质细胞亚型。脱髓鞘和神经退行性疾病引起具有不同分子特征和不同细胞动力学的上下文相关的小胶质细胞亚型。在健康人的大脑和多发性硬化症患者的大脑中也发现了相应的小胶质细胞簇。我们的数据提供了对中枢神经系统发育、动态平衡和疾病过程中内源性免疫系统的洞察，也可能为神经退行性和神经炎性病理的治疗提供新的靶点。
Microglia have critical roles not only in neural development and homeostasis, but also in neurodegenerative and neuroinflammatory diseases of the central nervous system(1-4). These highly diverse and specialized functions may be executed by subsets of microglia that already exist in situ, or by specific subsets of microglia that develop from a homogeneous pool of cells on demand. However, little is known about the presence of spatially and temporally restricted subclasses of microglia in the central nervous system during development or disease. Here we combine massively parallel single-cell analysis, single-molecule fluorescence in situ hybridization, advanced immunohistochemistry and computational modelling to comprehensively characterize subclasses of microglia in multiple regions of the central nervous system during development and disease. Single-cell analysis of tissues of the central nervous system during homeostasis in mice revealed specific time- and region-dependent subtypes of microglia. Demyelinating and neurodegenerative diseases evoked context-dependent subtypes of microglia with distinct molecular hallmarks and diverse cellular kinetics. Corresponding clusters of microglia were also identified in healthy human brains, and the brains of patients with multiple sclerosis. Our data provide insights into the endogenous immune system of the central nervous system during development, homeostasis and disease, and may also provide new targets for the treatment of neurodegenerative and neuroinflammatory pathologies.