Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes
Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes
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DOI：
10.1016/j.immuni.2018.11.004
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发表时间：
2019-01-15
期刊：
影响因子：
32.4
通讯作者：
Stevens, Beth
中科院分区：
文献类型：
--
作者：
Hammond, Timothy R.;Dufort, Connor;Stevens, Beth
小胶质细胞是大脑中的常驻免疫细胞，它们会迅速改变状态以应对环境，但我们缺乏不同小胶质细胞群体的分子和功能特征。在这里，我们分析了小鼠在发育过程中，老年和脑损伤后超过76，000个个体小胶质细胞的RNA表达模式。我们的分析揭示了至少九种转录上不同的小胶质细胞状态，它们表达了独特的基因组，并使用特定的标记物定位在大脑中。最大的小胶质细胞异质性发现在年轻的年龄，然而，几个国家，包括趋化因子丰富的炎性小胶质细胞持续整个生命周期或增加在老年大脑。在小鼠脱髓鞘损伤后也发现了多种反应性小胶质细胞亚型，其中至少一种也在人类多发性硬化症病变中发现。这些独特的小胶质细胞特征可用于更好地了解小胶质细胞功能，并识别和操纵健康和疾病中的特定亚群。
Microglia, the resident immune cells of the brain, rapidly change states in response to their environment, but we lack molecular and functional signatures of different microglial populations. Here, we analyzed the RNA expression patterns of more than 76,000 individual microglia in mice during development, in old age, and after brain injury. Our analysis uncovered at least nine transcriptionally distinct microglial states, which expressed unique sets of genes and were localized in the brain using specific markers. The greatest microglial heterogeneity was found at young ages; however, several states-including chemokine-enriched inflammatory microglia-persisted throughout the lifespan or increased in the aged brain. Multiple reactive microglial subtypes were also found following demyelinating injury in mice, at least one of which was also found in human multiple sclerosis lesions. These distinct microglia signatures can be used to better understand microglia function and to identify and manipulate specific subpopulations in health and disease.