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A single cell-based atlas of human microglial states reveals associations with neurological disorders and histopathological features of the aging brain

By Marta Olah, Vilas Menon, Naomi Habib, Mariko Taga, Christina Yung, Maria Cimpean, Anthony Khairalla, Danielle Dionne, Sarah Hopp, Matthew P Frosch, Bradley T Hyman, Thomas Beach, Rani Sarkis, Garth R Cosgrove, Jeffrey Helgager, Jeffrey A Golden, Page B Pennell, Julie A Schneider, David A. Bennett, Aviv Regev, Wassim Elyaman, Elizabeth M Bradshaw, Philip L De Jager

Posted 11 Jun 2018
bioRxiv DOI: 10.1101/343780

Recent studies of bulk microglia have provided insights into the role of this immune cell type in central nervous system development, homeostasis and dysfunction. Nonetheless, our understanding of the diversity of human microglial cell states remains limited. Microglia are highly plastic and have multiple different roles, making the extent of phenotypic heterogeneity a central question, especially in light of the development of therapies targeting this cell type. Here, we investigated the population structure of human microglia by single-cell RNA-sequencing. Using surgical- and autopsy-derived cortical brain samples, we identified 14 human microglial subpopulations and noted substantial intra- and inter-individual heterogeneity. These putative subpopulations display divergent associations with Alzheimer's disease, multiple sclerosis, and other diseases. Several states show enrichment for genes found in disease-associated mouse microglial states, suggesting additional diversity among human microglia. Overall, human microglia appear to exist in different functional states with varying levels of involvement in different brain pathologies.

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