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

Elife. 2020 Oct 15;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.

Keywords: Mac2; adult microglial progenitors; csf1r signaling; microglia; microglia homeostasis; mouse; myeloid cells; neuroscience.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / metabolism*
  • Female
  • Galectin 3 / genetics*
  • Galectin 3 / metabolism
  • Homeostasis
  • Male
  • Mice / genetics
  • Mice / physiology*
  • Mice, Inbred C57BL
  • Microglia / metabolism*
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Signal Transduction / genetics*

Substances

  • Csf1r protein, mouse
  • Galectin 3
  • Lgals3 protein, mouse
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor

Associated data

  • GEO/GSE150169