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健康和患病大脑中的小胶质细胞多样性:单细胞组学的新见解。

Microglia Diversity in Healthy and Diseased Brain: Insights from Single-Cell Omics.

机构信息

Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, Poland.

出版信息

Int J Mol Sci. 2021 Mar 16;22(6):3027. doi: 10.3390/ijms22063027.


DOI:10.3390/ijms22063027
PMID:33809675
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8002227/
Abstract

Microglia are the resident immune cells of the central nervous system (CNS) that have distinct ontogeny from other tissue macrophages and play a pivotal role in health and disease. Microglia rapidly react to the changes in their microenvironment. This plasticity is attributed to the ability of microglia to adapt a context-specific phenotype. Numerous gene expression profiling studies of immunosorted CNS immune cells did not permit a clear dissection of their phenotypes, particularly in diseases when peripheral cells of the immune system come to play. Only recent advances in single-cell technologies allowed studying microglia at high resolution and revealed a spectrum of discrete states both under homeostatic and pathological conditions. Single-cell technologies such as single-cell RNA sequencing (scRNA-seq) and mass cytometry (Cytometry by Time-Of-Flight, CyTOF) enabled determining entire transcriptomes or the simultaneous quantification of >30 cellular parameters of thousands of individual cells. Single-cell omics studies demonstrated the unforeseen heterogeneity of microglia and immune infiltrates in brain pathologies: neurodegenerative disorders, stroke, depression, and brain tumors. We summarize the findings from those studies and the current state of knowledge of functional diversity of microglia under physiological and pathological conditions. A precise definition of microglia functions and phenotypes may be essential to design future immune-modulating therapies.

摘要

小胶质细胞是中枢神经系统 (CNS) 的固有免疫细胞,它们与其他组织中的巨噬细胞有着明显不同的起源,并在健康和疾病中发挥着关键作用。小胶质细胞能迅速对其微环境的变化作出反应。这种可塑性归因于小胶质细胞适应特定环境表型的能力。对免疫分选的中枢免疫细胞进行的大量基因表达谱研究,未能清楚地区分它们的表型,尤其是在免疫系统的外周细胞开始发挥作用的疾病中。只有单细胞技术的最新进展,才使我们能够以高分辨率研究小胶质细胞,并揭示了在稳态和病理条件下,一系列离散状态。单细胞技术,如单细胞 RNA 测序 (scRNA-seq) 和液质流式细胞术 (Cytometry by Time-Of-Flight,CyTOF),使我们能够确定整个转录组,或同时对数千个单个细胞的 >30 个细胞参数进行定量。单细胞组学研究表明,在神经退行性疾病、中风、抑郁和脑肿瘤等脑病理中,小胶质细胞和免疫浸润存在着意想不到的异质性。我们总结了这些研究的发现,以及目前对小胶质细胞在生理和病理条件下功能多样性的认识。精确定义小胶质细胞的功能和表型,可能对于设计未来的免疫调节治疗至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac83/8002227/21a1d9e2c166/ijms-22-03027-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac83/8002227/51981562ca7c/ijms-22-03027-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac83/8002227/21a1d9e2c166/ijms-22-03027-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac83/8002227/51981562ca7c/ijms-22-03027-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac83/8002227/21a1d9e2c166/ijms-22-03027-g002.jpg

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本文引用的文献

[1]
Single-cell RNA sequencing reveals functional heterogeneity of glioma-associated brain macrophages.

Nat Commun. 2021-2-19

[2]
Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer's disease.

Nat Commun. 2020-11-30

[3]
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Transl Psychiatry. 2020-9-11

[4]
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Proc Natl Acad Sci U S A. 2020-9-8

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J Neuroinflammation. 2020-8-14

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Single-Cell Mapping of Human Brain Cancer Reveals Tumor-Specific Instruction of Tissue-Invading Leukocytes.

Cell. 2020-6-25

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JAMA Oncol. 2020-7-1

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Neurol Neuroimmunol Neuroinflamm. 2020-7

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Theranostics. 2020

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