Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer's disease
| Autor: | Andrew F. Teich, Danielle Dionne, Philip L. De Jager, Aviv Regev, Julie A. Schneider, Roman Sankowski, Jean Paul Vonsattel, Jeffrey Helgager, Jeffrey A. Golden, Marta Olah, Rani A. Sarkis, Dominic Grün, Vilas Menon, Wassim Elyaman, Naomi Habib, Elizabeth M. Bradshaw, Guillermo Coronas-Samano, Alexandra Kroshilina, Anthony Khairallah, Mariko Taga, David A. Bennett, Page B. Pennell, Christina J. Yung, Marco Prinz, Yiyi Ma, Garth Rees Cosgrove, Maria Cimpean |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Cell type Science Cell Neuroimmunology General Physics and Astronomy Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Cortex (anatomy) medicine Humans Myeloid Cells Gene Cerebral Cortex Multidisciplinary Microglia Sequence Analysis RNA RNA General Chemistry Alzheimer's disease 030104 developmental biology medicine.anatomical_structure nervous system Cerebral cortex Female Neuroscience Nucleus 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-18 (2020) |
| Popis: | The extent of microglial heterogeneity in humans remains a central yet poorly explored question in light of the development of therapies targeting this cell type. Here, we investigate the population structure of live microglia purified from human cerebral cortex samples obtained at autopsy and during neurosurgical procedures. Using single cell RNA sequencing, we find that some subsets are enriched for disease-related genes and RNA signatures. We confirm the presence of four of these microglial subpopulations histologically and illustrate the utility of our data by characterizing further microglial cluster 7, enriched for genes depleted in the cortex of individuals with Alzheimer’s disease (AD). Histologically, these cluster 7 microglia are reduced in frequency in AD tissue, and we validate this observation in an independent set of single nucleus data. Thus, our live human microglia identify a range of subtypes, and we prioritize one of these as being altered in AD. Imbalance of microglial phenotypes in the aging brain might underlie their involvement in late onset neurodegenerative diseases. Here we report the population structure of microglia in the aged human brain and the reduction of a particular microglia subset in individuals with Alzheimer’s disease . |
| Databáze: | OpenAIRE |
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