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. VonsattelAndrew F. Teich, Julie A. Schneider, David A. Bennett, Aviv Regev, Wassim Elyaman, Elizabeth M. Bradshaw, Philip L. De Jager*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

319 Scopus citations

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.

Original languageAmerican English
Article number6129
JournalNature Communications
Volume11
Issue number1
DOIs
StatePublished - Dec 2020

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

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