Transcriptomic analysis of purified human cortical microglia reveals age-associated changes
Transcriptomic analysis of purified human cortical microglia reveals age-associated changes
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DOI：
10.1038/nn.4597
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发表时间：
2017-08-01
影响因子：
25
通讯作者：
Eggen, Bart J. L.
中科院分区：
文献类型：
--
作者：
Galatro, Thais F.;Holtman, Inge R.;Eggen, Bart J. L.
小胶质细胞是中枢神经系统内稳态和先天神经免疫功能所必需的，在神经退行性变和脑老化中起着重要作用。在这里，我们介绍了从39名认知完整的人类受试者的顶叶皮质中分离纯化的小胶质细胞的基因表达谱。总体而言，人小胶质细胞表达的基因与小鼠相似，包括已建立的小胶质细胞基因CX3CR1、P2RY12和ITGAM(CD11b)。然而，许多免疫基因在人小胶质细胞中大量表达，包括TLR、F-cγ和Siglec受体，以及TAL1和IFI16，它们是增殖和细胞周期的调节因子，但这些基因并不是小鼠小胶质细胞特征的一部分。人类小胶质细胞中与年龄相关的变化丰富了涉及细胞黏附、轴突引导、细胞表面受体表达和肌动蛋白(DIS)组装的基因。在小鼠和人类之间观察到在衰老过程中调节的小胶质细胞基因的有限重叠，这表明人和小鼠的小胶质细胞衰老不同。
Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes CX3CR1, P2RY12 and ITGAM (CD11B). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including TLR, F-c gamma and SIGLEC receptors, as well as TAL1 and IFI16, regulators of proliferation and cell cycle. Age-associated changes in human microglia were enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression and actin (dis)assembly. Limited overlap was observed in microglial genes regulated during aging between mice and humans, indicating that human and mouse microglia age differently.