Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA Sequencing

Neuron. 2019 Jan 16;101(2):207-223.e10. doi: 10.1016/j.neuron.2018.12.006. Epub 2018 Dec 31.


Microglia are increasingly recognized for their major contributions during brain development and neurodegenerative disease. It is currently unknown whether these functions are carried out by subsets of microglia during different stages of development and adulthood or within specific brain regions. Here, we performed deep single-cell RNA sequencing (scRNA-seq) of microglia and related myeloid cells sorted from various regions of embryonic, early postnatal, and adult mouse brains. We found that the majority of adult microglia expressing homeostatic genes are remarkably similar in transcriptomes, regardless of brain region. By contrast, early postnatal microglia are more heterogeneous. We discovered a proliferative-region-associated microglia (PAM) subset, mainly found in developing white matter, that shares a characteristic gene signature with degenerative disease-associated microglia (DAM). Such PAM have amoeboid morphology, are metabolically active, and phagocytose newly formed oligodendrocytes. This scRNA-seq atlas will be a valuable resource for dissecting innate immune functions in health and disease.

Keywords: brain myeloid cells; brain regions; cell cycle; development; disease-associated microglia; heterogeneity; microglia; phagocytosis; proliferative-region-associated microglia; single-cell RNA-seq.

Publication types

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

MeSH terms

  • Algorithms
  • Animals
  • Animals, Newborn
  • Antigens, CD / metabolism
  • Brain* / cytology
  • Brain* / embryology
  • Brain* / growth & development
  • Cell Proliferation / physiology
  • Choroid Plexus / cytology
  • Cluster Analysis
  • Computer Simulation
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental / physiology*
  • Gene Regulatory Networks / physiology
  • High-Throughput Nucleotide Sequencing
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia / physiology*
  • Myeloid Cells / physiology*
  • Oligodendroglia / physiology
  • Phagocytosis / physiology
  • Sequence Analysis, RNA*
  • Transcriptome / physiology*


  • Antigens, CD