Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, Poland.
Int J Mol Sci. 2021 Mar 16;22(6):3027. doi: 10.3390/ijms22063027.
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.
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。
