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

By 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

Posted 01 Sep 2018
bioRxiv DOI: 10.1101/406363 (published DOI: 10.1016/j.neuron.2018.12.006)

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.

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