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

TitleA MAC2-positive progenitor-like microglial population is resistant to CSF1R inhibition in adult mouse brain.
Publication TypeJournal Article
Year of Publication2020
AuthorsZhan L, Fan L, Kodama L, Sohn PDongmin, Wong MYing, Mousa GAlzaem, Zhou Y, Li Y, Gan L
JournalElife
Volume9
Date Published2020 Oct 15
ISSN2050-084X
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.

DOI10.7554/eLife.51796
Alternate JournalElife
PubMed ID33054973
Grant List1R01AG054214-01A1 / 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