A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment

Nat Neurosci. 2019 Jun;22(6):1021-1035. doi: 10.1038/s41593-019-0393-4. Epub 2019 May 6.


While the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less well understood. By dissecting border regions and combining single-cell RNA-sequencing with high-dimensional cytometry, bulk RNA-sequencing, fate-mapping and microscopy, we reveal the diversity of non-parenchymal brain macrophages. Border-associated macrophages (BAMs) residing in the dura mater, subdural meninges and choroid plexus consisted of distinct subsets with tissue-specific transcriptional signatures, and their cellular composition changed during postnatal development. BAMs exhibited a mixed ontogeny, and subsets displayed distinct self-renewal capacity following depletion and repopulation. Single-cell and fate-mapping analysis both suggested that there is a unique microglial subset residing on the apical surface of the choroid plexus epithelium. Finally, gene network analysis and conditional deletion revealed IRF8 as a master regulator that drives the maturation and diversity of brain macrophages. Our results provide a framework for understanding host-macrophage interactions in both the healthy and diseased brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology*
  • Cell Differentiation / physiology
  • Cell Lineage / physiology
  • Female
  • Interferon Regulatory Factors / metabolism*
  • Macrophages / cytology*
  • Macrophages / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / cytology


  • Interferon Regulatory Factors
  • interferon regulatory factor-8