阿尔茨海默病中的小胶质细胞异质性:来自单细胞技术的见解

Microglia Heterogeneity in Alzheimer's Disease: Insights From Single-Cell Technologies.

作者信息

Wang Hansen

机构信息

Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.

出版信息

Front Synaptic Neurosci. 2021 Dec 23;13:773590. doi: 10.3389/fnsyn.2021.773590. eCollection 2021.

Abstract

Microglia are resident immune cells in the central nervous system and play critical roles in brain immunity, development, and homeostasis. The pathology of Alzheimer's disease (AD) triggers activation of microglia. Microglia express many AD risk genes, suggesting that their response to AD pathology can affect disease progression. Microglia have long been considered a homogenous cell population. The diversity of microglia has gained great interest in recent years due to the emergence of novel single-cell technologies, such as single-cell/nucleus RNA sequencing and single-cell mass cytometry by time-of-flight. This review summarizes the current knowledge about the diversity/heterogeneity of microglia and distinct microglia states in the brain of both AD mouse models and patients, as revealed by single-cell technologies. It also discusses the future developments for application of single-cell technologies and the integration of these technologies with functional studies to further dissect microglia biology in AD. Defining the functional correlates of distinct microglia states will shed new light on the pathological roles of microglia and might uncover new relevant therapeutic targets for AD.

摘要

小胶质细胞是中枢神经系统中的常驻免疫细胞,在脑免疫、发育和内环境稳态中发挥关键作用。阿尔茨海默病(AD)的病理学特征会触发小胶质细胞的激活。小胶质细胞表达许多AD风险基因,这表明它们对AD病理学特征的反应会影响疾病进展。长期以来,小胶质细胞一直被认为是一种同质细胞群体。近年来,由于新型单细胞技术的出现,如单细胞/细胞核RNA测序和飞行时间单细胞质谱流式细胞术,小胶质细胞的多样性引起了人们极大的兴趣。本综述总结了通过单细胞技术揭示的关于AD小鼠模型和患者大脑中小胶质细胞多样性/异质性以及不同小胶质细胞状态的当前知识。它还讨论了单细胞技术应用的未来发展以及这些技术与功能研究的整合,以进一步剖析AD中小胶质细胞生物学特性。定义不同小胶质细胞状态的功能相关性将为小胶质细胞的病理作用提供新的线索,并可能揭示AD新的相关治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77e3/8735255/abbc2f3419c4/fnsyn-13-773590-g001.jpg

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