A single cell-based atlas of human microglial states reveals associations with neurological disorders and histopathological features of the aging brain
| Autor: | B. T. Hyman, Sarah C. Hopp, Jeffrey Helgager, Julie A. Schneider, Jeffrey A. Golden, Mariko Taga, Rani A. Sarkis, Garth Rees Cosgrove, Maria Cimpean, Marta Olah, Naomi Habib, Khairalla A, Aviv Regev, Matthew P. Frosch, Christina J. Yung, Elizabeth M. Bradshaw, David A. Bennett, Danielle Dionne, Wassim Elyaman, Thomas G. Beach, Page B. Pennell, De Jager Pl, Menon |
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| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
Cell type Microglia Genetic heterogeneity Multiple sclerosis Central nervous system Disease Biology medicine.disease 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Immune system medicine Aging brain Neuroscience 030217 neurology & neurosurgery 030304 developmental biology |
| DOI: | 10.1101/343780 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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