A MAC2-positive progenitor-like microglial population is resistant to CSF1R inhibition in adult mouse brain
- Gladstone Institutes, United States
- Weill Cornell Medicine, United States
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/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.
Data availability
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).
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scRNA-seqNCBI Gene Expression Omnibus, GSE150169.
Article and author information
Author details
Funding
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.
Ethics
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.
Reviewing Editor
- Beth Stevens, Boston Children's Hospital, United States
Version history
- 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)
Copyright
© 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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A MAC2-positive progenitor-like microglial population is resistant to CSF1R inhibition in adult mouse brain
eLife 9:e51796.
https://doi.org/10.7554/eLife.51796
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