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

By Qingyun Li, Zuolin Cheng, Lu Zhou, S. Darmanis, N. Neff, Jennifer Okamoto, G. Gulati, Mariko L. Bennett, Lu O. Sun, L. Clarke and 5 more. bioRxiv, 2018

944 citations recorded by the source corpus.

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 stages Limited transcriptomic heterogeneity of homeostatic microglia in the adult brain Phase-specific gene sets of proliferating microglia along cell cycle pseudotime Phagocytic postnatal white matter-associated microglia sharing DAM gene signatures

Subfields: Immunology, Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/270b4eae7c1a541784465515af0953c5981ff9c2

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Citations in the corpus

Lipid droplet accumulating microglia represent a dysfunctional and pro-inflammatory state in the aging brain (2019, methodology): “Lastly, we compared the transcriptional profile of LD-hi microglia with that of microglia in aging(40), ALS(41), and AD(42), and of microglia subpopulations recently identified in development, aging and disease, including “disease-associated microglia” (DAM)(12), “neurodegenerative microglia” (MGnD)”
Robust mapping of spatiotemporal trajectories and cell–cell interactions in healthy and diseased tissues (2023, neutral): “Under steady-state conditions, these resident macrophage-like cells of the brain display little heterogeneity between different brain regions and have a mostly rami ﬁ ed phenotype 26,27 .”
Microglia states and nomenclature: A field at its crossroads (2022, positive): “68,69,91 Relatively small transcriptional differences may, however, lead to relevant functional differences, as exempliﬁed by the functional variations between hippocampal and cerebellar microglia.”