PT  - JOURNAL ARTICLE
AU  - Qingyun Li
AU  - Zuolin Cheng
AU  - Lu Zhou
AU  - Spyros Darmanis
AU  - Norma Neff
AU  - Jennifer Okamoto
AU  - Gunsagar Gulati
AU  - Mariko L. Bennett
AU  - Lu O. Sun
AU  - Laura E. Clarke
AU  - Julia Marschallinger
AU  - Guoqiang Yu
AU  - Stephen R. Quake
AU  - Tony Wyss-Coray
AU  - Ben A. Barres
TI  - Developmental heterogeneity of microglia and brain myeloid cells revealed by deep single-cell RNA sequencing
AID  - 10.1101/406363
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 406363
4099  - http://biorxiv.org/content/early/2018/09/01/406363.short
4100  - http://biorxiv.org/content/early/2018/09/01/406363.full
AB  - 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.HighlightsMyeloid 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