A MAC2-positive progenitor-like microglial population is resistant to CSF1R inhibition in adult mouse brain
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.
The raw count matrix of the scRNA-seq data can be accessed on GEO with accession number (GSE150169). A list of R codes used for the analyses are available on Github (https://github.com/lifan36/Zhan-Fan-et-al-2019-scRNAseq).
scRNA-seqNCBI Gene Expression Omnibus, GSE150169.
Article and author information
National Institutes of Health (1R01AG054214-01A1)
- Li Gan
National Institutes of Health (U54NS100717)
- Li Gan
National Institutes of Health (R01AG051390)
- Li Gan
Tau Consortium grant
- Li Gan
National Institute of Aging (F30 AG062043-02)
- Lay Kodama
National Institutes of Health (T32GM007618)
- 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)
- Version of Record published: October 27, 2020 (version 2)
© 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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