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The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions

Author

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  • Ricardo Martins-Ferreira

    (08916 Badalona
    4050-313
    University of Porto
    ITR - Laboratory for Integrative and Translational Research in Population Health)

  • Josep Calafell-Segura

    (08916 Badalona)

  • Bárbara Leal

    (4050-313
    University of Porto
    ITR - Laboratory for Integrative and Translational Research in Population Health)

  • Javier Rodríguez-Ubreva

    (08916 Badalona)

  • Elena Martínez-Saez

    (Universitat Autònoma de Barcelona)

  • Elisabetta Mereu

    (08916 Badalona)

  • Paulo Pinho E Costa

    (4050-313
    University of Porto
    ITR - Laboratory for Integrative and Translational Research in Population Health
    4000-055)

  • Ariadna Laguna

    (Vall d’Hebron Research Institute (VHIR)-Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)
    Institut de Neurociències-Autonomous University of Barcelona (INc-UAB))

  • Esteban Ballestar

    (08916 Badalona
    East China Normal University (ECNU))

Abstract

Dysregulated microglia activation, leading to neuroinflammation, is crucial in neurodegenerative disease development and progression. We constructed an atlas of human brain immune cells by integrating nineteen single-nucleus RNA-seq and single-cell RNA-seq datasets from multiple neurodegenerative conditions, comprising 241 samples from patients with Alzheimer’s disease, autism spectrum disorder, epilepsy, multiple sclerosis, Lewy body diseases, COVID-19, and healthy controls. The integrated Human Microglia Atlas (HuMicA) included 90,716 nuclei/cells and revealed nine populations distributed across all conditions. We identified four subtypes of disease-associated microglia and disease-inflammatory macrophages, recently described in mice, and shown here to be prevalent in human tissue. The high versatility of microglia is evident through changes in subset distribution across various pathologies, suggesting their contribution in shaping pathological phenotypes. A GPNMB-high subpopulation was expanded in AD and MS. In situ hybridization corroborated this increase in AD, opening the question on the relevance of this population in other pathologies.

Suggested Citation

  • Ricardo Martins-Ferreira & Josep Calafell-Segura & Bárbara Leal & Javier Rodríguez-Ubreva & Elena Martínez-Saez & Elisabetta Mereu & Paulo Pinho E Costa & Ariadna Laguna & Esteban Ballestar, 2025. "The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56124-1
    DOI: 10.1038/s41467-025-56124-1
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