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.
- Li Gan
- Li Gan
- Li Gan
- Li Gan
- Lay Kodama
- Lay Kodama
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#AN173162-02) of the University of California, San Francisco.
- Beth Stevens, Boston Children's Hospital, United States
- Received: September 11, 2019
- Accepted: October 14, 2020
- Accepted Manuscript published: October 15, 2020 (version 1)
© 2020, Zhan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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