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A MAC2-positive progenitor-like microglial population is resistant to CSF1R inhibition in adult mouse brain
oleh: Lihong Zhan, Li Fan, Lay Kodama, Peter Dongmin Sohn, Man Ying Wong, Gergey Alzaem Mousa, Yungui Zhou, Yaqiao Li, Li Gan
Format: | Article |
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Diterbitkan: | eLife Sciences Publications Ltd 2020-10-01 |
Deskripsi
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.