Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease

Olah M, Menon V, Habib N, Taga MF, Ma Y, Yung CJ, Cimpean M, Khairallah A, Coronas-Samano G, Sankowski R, Gruen D, Kroshilina AA, Dionne D, Sarkis RA, Cosgrove GR, Helgager J, Golden JA, Pennell PB, Prinz M, Vonsattel JPG, Teich AF, Schneider JA, Bennett DA, Regev A, Elyaman W, Bradshaw EM, De Jager PL (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 11

Article Number: 6129

Journal Issue: 1

DOI: 10.1038/s41467-020-19737-2

Abstract

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.

Involved external institutions

Columbia University US United States (USA) (US) Eli and Edythe L. Broad Institute of MIT and Harvard US United States (USA) (US) Brigham and Women's Hospital (BWH) US United States (USA) (US) Albert-Ludwigs-Universität Freiburg DE Germany (DE) Rush University US United States (USA) (US) Max-Planck-Institut für Immunbiologie und Epigenetik (MPI-IE) / Max Planck Institute of Immunobiology and Epigenetics DE Germany (DE)

How to cite

APA:

Olah, M., Menon, V., Habib, N., Taga, M.F., Ma, Y., Yung, C.J.,... De Jager, P.L. (2020). Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease. Nature Communications, 11(1). https://doi.org/10.1038/s41467-020-19737-2

MLA:

Olah, Marta, et al. "Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease." Nature Communications 11.1 (2020).

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