Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion

Nat Neurosci. 2018 Apr;21(4):530-540. doi: 10.1038/s41593-018-0090-8. Epub 2018 Feb 22.

Abstract

Newborn microglia rapidly replenish the whole brain after selective elimination of most microglia (>99%) in adult mice. Previous studies reported that repopulated microglia were largely derived from microglial progenitor cells expressing nestin in the brain. However, the origin of these repopulated microglia has been hotly debated. In this study, we investigated the origin of repopulated microglia by a series of fate-mapping approaches. We first excluded the blood origin of repopulated microglia via parabiosis. With different transgenic mouse lines, we then demonstrated that all repopulated microglia were derived from the proliferation of the few surviving microglia (<1%). Despite a transient pattern of nestin expression in newly forming microglia, none of repopulated microglia were derived from nestin-positive non-microglial cells. In summary, we conclude that repopulated microglia are solely derived from residual microglia rather than de novo progenitors, suggesting the absence of microglial progenitor cells in the adult brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / physiology
  • Brain / cytology*
  • Brain / drug effects
  • CX3C Chemokine Receptor 1 / genetics
  • CX3C Chemokine Receptor 1 / metabolism
  • Calcium-Binding Proteins / metabolism
  • Cell Lineage
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology*
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Lipopolysaccharides / pharmacology
  • Macrophage Colony-Stimulating Factor / antagonists & inhibitors
  • Macrophage Colony-Stimulating Factor / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microfilament Proteins / metabolism
  • Microglia / drug effects
  • Microglia / physiology*
  • Neurogenesis / drug effects
  • Neurogenesis / physiology*
  • Organic Chemicals / pharmacology
  • Stem Cells / drug effects
  • Stem Cells / physiology
  • Transcriptome / drug effects
  • Transcriptome / physiology

Substances

  • Actins
  • Aif1 protein, mouse
  • CX3C Chemokine Receptor 1
  • Calcium-Binding Proteins
  • Cx3cr1 protein, mouse
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • Microfilament Proteins
  • Organic Chemicals
  • PLX5622
  • Macrophage Colony-Stimulating Factor