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人类皮质小胶质细胞的转录组分析揭示了与年龄相关的变化。

Transcriptomic analysis of purified human cortical microglia reveals age-associated changes.

机构信息

Department of Neuroscience, Section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Department of Neurology, Laboratory of Molecular and Cellular Biology, School of Medicine, University of São Paulo, São Paulo, Brazil.

出版信息

Nat Neurosci. 2017 Aug;20(8):1162-1171. doi: 10.1038/nn.4597. Epub 2017 Jul 3.

DOI:10.1038/nn.4597
PMID:28671693
Abstract

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, Fcγ 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.

摘要

小胶质细胞对于中枢神经系统的稳态和先天神经免疫功能至关重要,并且在神经退行性变和大脑衰老中发挥着重要作用。在这里,我们展示了从 39 名认知功能正常的人类尸检大脑顶叶中分离的纯化小胶质细胞的基因表达谱。总体而言,人类小胶质细胞表达的基因与小鼠中的相似,包括已确定的小胶质细胞基因 CX3CR1、P2RY12 和 ITGAM(CD11B)。然而,许多免疫基因,这些基因没有被鉴定为小鼠小胶质细胞特征的一部分,在人类小胶质细胞中大量表达,包括 TLR、Fcγ 和 SIGLEC 受体,以及 TAL1 和 IFI16,这些基因是增殖和细胞周期的调节剂。与人类小胶质细胞衰老相关的变化富集了与细胞黏附、轴突导向、细胞表面受体表达和肌动蛋白(解)组装相关的基因。在小鼠和人类衰老过程中调节的小胶质细胞基因之间观察到的重叠有限,表明人类和小鼠的小胶质细胞衰老方式不同。

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