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在成年小鼠大脑中，MAC2 阳性祖细胞样小胶质细胞群体对 CSF1R 抑制具有抗性。

A MAC2-positive progenitor-like microglial population is resistant to CSF1R inhibition in adult mouse brain.

机构信息

Gladstone Institute of Neurological Diseases, San Francisco, United States.

Helen and Robert Appel Alzheimer's Disease Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York, United States.

出版信息

Elife. 2020 Oct 15;9:e51796. doi: 10.7554/eLife.51796.

DOI:10.7554/eLife.51796
PMID:33054973
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7591254/
Abstract

Microglia are the resident myeloid cells in the central nervous system (CNS). The majority of microglia rely on CSF1R signaling for survival. However, a small subset of microglia in mouse brains can survive without CSF1R signaling and reestablish the microglial homeostatic population after CSF1R signaling returns. Using single-cell transcriptomic analysis, we characterized the heterogeneous microglial populations under CSF1R inhibition, including microglia with reduced homeostatic markers and elevated markers of inflammatory chemokines and proliferation. Importantly, MAC2/ was upregulated under CSF1R inhibition, and shared striking similarities with microglial progenitors in the yolk sac and immature microglia in early embryos. Lineage-tracing studies revealed that these MAC2+ cells were of microglial origin. MAC2+ microglia were also present in non-treated adult mouse brains and exhibited immature transcriptomic signatures indistinguishable from those that survived CSF1R inhibition, supporting the notion that MAC2+ progenitor-like cells are present among adult microglia.

摘要

小胶质细胞是中枢神经系统（CNS）中的固有髓样细胞。大多数小胶质细胞依赖 CSF1R 信号存活。然而，在小鼠大脑中，一小部分小胶质细胞可以在没有 CSF1R 信号的情况下存活，并在 CSF1R 信号恢复后重建小胶质细胞的稳态群体。使用单细胞转录组分析，我们对 CSF1R 抑制下的异质小胶质细胞群体进行了特征描述，包括具有降低的稳态标志物和升高的炎症趋化因子和增殖标志物的小胶质细胞。重要的是，MAC2/在 CSF1R 抑制下上调，并与卵黄囊中的小胶质细胞前体细胞和早期胚胎中的未成熟小胶质细胞具有惊人的相似性。谱系追踪研究表明，这些 MAC2+细胞源自小胶质细胞。MAC2+小胶质细胞也存在于未经处理的成年小鼠大脑中，并表现出与 CSF1R 抑制后存活的细胞相似的未成熟转录组特征，支持 MAC2+祖细胞样细胞存在于成年小胶质细胞中的观点。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d0/7591254/dd1d74019dc0/elife-51796-resp-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d0/7591254/e9badea518e5/elife-51796-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d0/7591254/d73635b4718e/elife-51796-fig5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d0/7591254/e31227c1e205/elife-51796-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d0/7591254/a16167e84cf2/elife-51796-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d0/7591254/fe7b348bbb07/elife-51796-fig7.jpg
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