Developmental heterogeneity of microglia and brain myeloid cells revealed by deep single-cell RNA sequencing

Qingyun Li, Zuolin Cheng, Lu Zhou, Spyros Darmanis, Norma 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

Abstract

Microglia are increasingly recognized for their major contributions during brain development and neurodegenerative disease. It is currently unknown if 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, postnatal, and adult mouse brains. We found that the majority of adult microglia with homeostatic signatures are remarkably similar in transcriptomes, regardless of brain region. By contrast, postnatal microglia represent a more heterogeneous population. We discovered that postnatal white matter-associated microglia (WAM) are strikingly different from microglia in other regions and express genes enriched in degenerative disease-associated microglia. These postnatal WAM have distinct 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. Highlights Myeloid scRNA-seq atlas across brain regions and developmental stagesLimited transcriptomic heterogeneity of homeostatic microglia in the adult brainPhase-specific gene sets of proliferating microglia along cell cycle pseudotimePhagocytic postnatal white matter-associated microglia sharing DAM gene signatures

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Sep 1 2018
Externally publishedYes

Keywords

  • brain myeloid cells
  • brain regions
  • cell cycle
  • development
  • disease-associated microglia
  • heterogeneity
  • microglia
  • phagocytosis
  • postnatal white matter-associated microglia
  • single-cell RNA-seq

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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