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

Marta Olah, Vilas Menon, Naomi Habib, Mariko F. Taga, Yiyi Ma, Christina J. Yung, Maria Cimpean, Anthony Khairallah, Guillermo Coronas-Samano, Roman Sankowski, Dominic Grün, Alexandra A. Kroshilina, Danielle Dionne, Rani A. Sarkis, Garth R. Cosgrove, Jeffrey Helgager, Jeffrey A. Golden, Page B. Pennell, Marco Prinz, Jean Paul G. Vonsattel, Andrew F. Teich, Julie A. Schneider, David A. Bennett, Aviv Regev, Wassim Elyaman, Elizabeth M. Bradshaw and Philip L. Jager ()
Additional contact information
Marta Olah: Columbia University Medical Center
Vilas Menon: Columbia University Medical Center
Naomi Habib: Broad Institute
Mariko F. Taga: Columbia University Medical Center
Yiyi Ma: Columbia University Medical Center
Christina J. Yung: Columbia University Medical Center
Maria Cimpean: Columbia University Medical Center
Anthony Khairallah: Columbia University Medical Center
Guillermo Coronas-Samano: Columbia University Medical Center
Roman Sankowski: University of Freiburg
Dominic Grün: Max-Planck-Institute of Immunobiology and Epigenetics
Alexandra A. Kroshilina: Columbia University Medical Center
Danielle Dionne: Broad Institute
Rani A. Sarkis: Brigham and Women’s Hospital
Garth R. Cosgrove: Brigham and Women’s Hospital
Jeffrey Helgager: Brigham and Women’s Hospital
Jeffrey A. Golden: Brigham and Women’s Hospital
Page B. Pennell: Brigham and Women’s Hospital
Marco Prinz: University of Freiburg
Jean Paul G. Vonsattel: Columbia University Medical Center
Andrew F. Teich: Columbia University Medical Center
Julie A. Schneider: Rush University Medical Center
David A. Bennett: Rush University Medical Center
Aviv Regev: Broad Institute
Wassim Elyaman: Columbia University Medical Center
Elizabeth M. Bradshaw: Columbia University Medical Center
Philip L. Jager: Columbia University Medical Center

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19737-2

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