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

Qingyun Li, Zuolin Cheng, Lu Zhou, Spyros Darmanis, Norma F. Neff, Jennifer Okamoto, Gunsagar Gulati, Mariko L. Bennett, Lu O. Sun, Laura E. Clarke, Julia Marschallinger, Guoqiang Yu, Stephen R. Quake, Tony Wyss-Coray, Ben A. Barres

Research output: Contribution to journalArticlepeer-review

131 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)207-223.e10
JournalNeuron
Volume101
Issue number2
DOIs
StatePublished - Jan 16 2019
Externally publishedYes

Keywords

  • brain myeloid cells
  • brain regions
  • cell cycle
  • development
  • disease-associated microglia
  • heterogeneity
  • microglia
  • phagocytosis
  • proliferative-region-associated microglia
  • single-cell RNA-seq

ASJC Scopus subject areas

  • Neuroscience(all)

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