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

  1. Lihong Zhan
  2. Li Fan
  3. Lay Kodama
  4. Peter Dongmin Sohn
  5. Man Ying Wong
  6. Gergey Alzaem Mousa
  7. Yungui Zhou
  8. Yaqiao Li
  9. Li Gan  Is a corresponding author
  1. Gladstone Institutes, United States
  2. Weill Cornell Medicine, United States
Research Article
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Cite this article as: eLife 2020;9:e51796 doi: 10.7554/eLife.51796

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.

Article and author information

Author details

  1. Lihong Zhan

    Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, United States
    Competing interests
    No competing interests declared.
  2. Li Fan

    Helen and Robert Appel Alzheimer's Disease Institute, Weill Cornell Medicine, New York, United States
    Competing interests
    No competing interests declared.
  3. Lay Kodama

    Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, United States
    Competing interests
    No competing interests declared.
  4. Peter Dongmin Sohn

    Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, United States
    Competing interests
    No competing interests declared.
  5. Man Ying Wong

    Helen and Robert Appel Alzheimer's Disease Institute, Weill Cornell Medicine, New York, United States
    Competing interests
    No competing interests declared.
  6. Gergey Alzaem Mousa

    Helen and Robert Appel Alzheimer's Disease Institute, Weill Cornell Medicine, New York, United States
    Competing interests
    No competing interests declared.
  7. Yungui Zhou

    Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, United States
    Competing interests
    No competing interests declared.
  8. Yaqiao Li

    Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, United States
    Competing interests
    No competing interests declared.
  9. Li Gan

    Helen and Robert Appel Alzheimer's Disease Institute, Weill Cornell Medicine, New York, United States
    For correspondence
    lig2033@med.cornell.edu
    Competing interests
    Li Gan, Li Gan is a founder of Aeton Therapeutics, Inc..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4600-275X

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

  1. Beth Stevens, Boston Children's Hospital, United States

Publication history

  1. Received: September 11, 2019
  2. Accepted: October 14, 2020
  3. Accepted Manuscript published: October 15, 2020 (version 1)

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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