Subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave

Elife. 2021 Aug 23;10:e66738. doi: 10.7554/eLife.66738.


Microglia, the brain's resident myeloid cells, play central roles in brain defense, homeostasis, and disease. Using a prolonged colony-stimulating factor 1 receptor inhibitor (CSF1Ri) approach, we report an unprecedented level of microglial depletion and establish a model system that achieves an empty microglial niche in the adult brain. We identify a myeloid cell that migrates from the subventricular zone and associated white matter areas. Following CSF1Ri, these amoeboid cells migrate radially and tangentially in a dynamic wave filling the brain in a distinct pattern, to replace the microglial-depleted brain. These repopulating cells are enriched in disease-associated microglia genes and exhibit similar phenotypic and transcriptional profiles to white-matter-associated microglia. Our findings shed light on the overlapping and distinct functional complexity and diversity of myeloid cells of the CNS and provide new insight into repopulating microglia function and dynamics in the mouse brain.

Keywords: CSF1R; depletion; immunology; inflammation; microglia; mouse; neuroscience; repopulation; white matter.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain
  • Disease Models, Animal
  • Homeostasis
  • Inflammation
  • Lateral Ventricles / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / physiology*
  • Myeloid Cells / cytology
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • White Matter / physiology*


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

Associated data

  • GEO/GSE166092