A MAC2-positive progenitor-like microglial population is resistant to CSF1R inhibition in adult mouse brain.
A MAC2-positive progenitor-like microglial population is resistant to CSF1R inhibition in adult mouse brain.
复制标题
MAC2阳性祖细胞样小胶质细胞种群对成年小鼠大脑的CSF1R抑制具有抗性。
作者：
Zhan L;Fan L;Kodama L;Sohn PD;Wong MY;Mousa GA;Zhou Y;Li Y;Gan L
小胶质细胞是中枢神经系统（CNS）中的常驻髓样细胞。大多数小胶质细胞依赖于CSF 1 R信号传导来存活。然而，小鼠大脑中的小胶质细胞的一小部分可以在没有CSF 1 R信号的情况下存活，并在CSF 1 R信号恢复后重新建立小胶质细胞稳态群体。使用单细胞转录组学分析，我们表征了CSF 1 R抑制下的异质性小胶质细胞群体，包括具有降低的稳态标志物和升高的炎性趋化因子和增殖标志物的小胶质细胞。重要的是，MAC 2/Lgals 3在CSF 1 R抑制下上调，并且与卵黄囊中的小胶质祖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MAC 2+细胞的小胶质细胞的起源。MAC 2+小胶质细胞也存在于未处理的成年小鼠脑中，并显示出与CSF 1 R抑制后存活的未成熟转录组特征无法区分的未成熟转录组特征，支持MAC 2+祖细胞样细胞存在于成年小胶质细胞中的观点。
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/Lgals3 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.