Title | A MAC2-positive progenitor-like microglial population is resistant to CSF1R inhibition in adult mouse brain. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Zhan L, Fan L, Kodama L, Sohn PDongmin, Wong MYing, Mousa GAlzaem, Zhou Y, Li Y, Gan L |
Journal | Elife |
Volume | 9 |
Date Published | 2020 Oct 15 |
ISSN | 2050-084X |
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. |
DOI | 10.7554/eLife.51796 |
Alternate Journal | Elife |
PubMed ID | 33054973 |
Grant List | 1R01AG054214-01A1 / NH / NIH HHS / United States U54NS100717 / NH / NIH HHS / United States R01AG051390 / NH / NIH HHS / United States F30 AG062043-02 / / National Institute of Aging / T32GM007618 / NH / NIH HHS / United States |