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

Author

Listed:
  • Marta Olah

    (Columbia University Medical Center
    Columbia University Medical Center
    Columbia University Medical Center
    Broad Institute)

  • Vilas Menon

    (Columbia University Medical Center
    Columbia University Medical Center
    Columbia University Medical Center
    Broad Institute)

  • Naomi Habib

    (Broad Institute
    The Hebrew University of Jerusalem)

  • Mariko F. Taga

    (Columbia University Medical Center
    Columbia University Medical Center
    Columbia University Medical Center
    Broad Institute)

  • Yiyi Ma

    (Columbia University Medical Center
    Columbia University Medical Center
    Columbia University Medical Center
    Broad Institute)

  • 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
    Columbia University Medical Center)

  • Roman Sankowski

    (University of Freiburg
    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
    University of Freiburg
    University of Freiburg)

  • Jean Paul G. Vonsattel

    (Columbia University Medical Center
    Columbia University Medical Center)

  • Andrew F. Teich

    (Columbia University Medical Center
    Columbia University Medical Center
    Columbia University Medical Center)

  • Julie A. Schneider

    (Rush University Medical Center)

  • David A. Bennett

    (Rush University Medical Center)

  • Aviv Regev

    (Broad Institute
    Broad Institute of MIT and Harvard
    Department of Biology, MIT
    Genentech, 1 DNA Way)

  • Wassim Elyaman

    (Columbia University Medical Center
    Columbia University Medical Center
    Broad Institute)

  • Elizabeth M. Bradshaw

    (Columbia University Medical Center
    Columbia University Medical Center
    Broad Institute)

  • Philip L. Jager

    (Columbia University Medical Center
    Columbia University Medical Center
    Columbia University Medical Center
    Broad Institute)

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.

Suggested Citation

  • 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. Kr, 2020. "Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19737-2
    DOI: 10.1038/s41467-020-19737-2
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    Cited by:

    1. Vicky Chou & Richard V. Pearse & Aimee J. Aylward & Nancy Ashour & Mariko Taga & Gizem Terzioglu & Masashi Fujita & Seeley B. Fancher & Alina Sigalov & Courtney R. Benoit & Hyo Lee & Matti Lam & Nicho, 2023. "INPP5D regulates inflammasome activation in human microglia," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    2. Shannon Tansley & Sonali Uttam & Alba Ureña Guzmán & Moein Yaqubi & Alain Pacis & Marc Parisien & Haley Deamond & Calvin Wong & Oded Rabau & Nicole Brown & Lisbet Haglund & Jean Ouellet & Carlo Santag, 2022. "Single-cell RNA sequencing reveals time- and sex-specific responses of mouse spinal cord microglia to peripheral nerve injury and links ApoE to chronic pain," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Erik Nutma & Nurun Fancy & Maria Weinert & Stergios Tsartsalis & Manuel C. Marzin & Robert C. J. Muirhead & Irene Falk & Marjolein Breur & Joy Bruin & David Hollaus & Robin Pieterman & Jasper Anink & , 2023. "Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases," Nature Communications, Nature, vol. 14(1), pages 1-25, December.
    4. Logan Brase & Shih-Feng You & Ricardo D’Oliveira Albanus & Jorge L. Del-Aguila & Yaoyi Dai & Brenna C. Novotny & Carolina Soriano-Tarraga & Taitea Dykstra & Maria Victoria Fernandez & John P. Budde & , 2023. "Single-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    5. Ashley Byrne & Daniel Le & Kostianna Sereti & Hari Menon & Samir Vaidya & Neha Patel & Jessica Lund & Ana Xavier-Magalhães & Minyi Shi & Yuxin Liang & Timothy Sterne-Weiler & Zora Modrusan & William S, 2024. "Single-cell long-read targeted sequencing reveals transcriptional variation in ovarian cancer," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    6. Jiyeon Lee & Julie M. Dimitry & Jong Hee Song & Minsoo Son & Patrick W. Sheehan & Melvin W. King & G. Travis Tabor & Young Ah Goo & Mitchell A. Lazar & Leonard Petrucelli & Erik S. Musiek, 2023. "Microglial REV-ERBα regulates inflammation and lipid droplet formation to drive tauopathy in male mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Minhui Chen & Andy Dahl, 2024. "A robust model for cell type-specific interindividual variation in single-cell RNA sequencing data," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    8. Lindsey R. Conroy & Harrison A. Clarke & Derek B. Allison & Samuel Santos Valenca & Qi Sun & Tara R. Hawkinson & Lyndsay E. A. Young & Juanita E. Ferreira & Autumn V. Hammonds & Jaclyn B. Dunne & Robe, 2023. "Spatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    9. Özkan İş & Xue Wang & Joseph S. Reddy & Yuhao Min & Elanur Yilmaz & Prabesh Bhattarai & Tulsi Patel & Jeremiah Bergman & Zachary Quicksall & Michael G. Heckman & Frederick Q. Tutor-New & Birsen Can De, 2024. "Gliovascular transcriptional perturbations in Alzheimer’s disease reveal molecular mechanisms of blood brain barrier dysfunction," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    10. Romain Sigaud & Thomas K. Albert & Caroline Hess & Thomas Hielscher & Nadine Winkler & Daniela Kocher & Carolin Walter & Daniel Münter & Florian Selt & Diren Usta & Jonas Ecker & Angela Brentrup & Mar, 2023. "MAPK inhibitor sensitivity scores predict sensitivity driven by the immune infiltration in pediatric low-grade gliomas," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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