The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions
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.
Authors
- Paulo Costa (ORCID: https://orcid.org/0000-0001-6125-7000)
- Bárbara Leal (ORCID: https://orcid.org/0000-0003-0936-4719)
- Josep Calafell-Segura (ORCID: https://orcid.org/0000-0002-0173-8221)
- Ricardo Martins-Ferreira (ORCID: https://orcid.org/0000-0001-9337-1860)
- Ariadna Laguna (ORCID: https://orcid.org/0000-0002-9732-6677)
- Javier Rodríguez‐Ubreva (ORCID: https://orcid.org/0000-0003-4707-4536)
- Elisabetta Mereu (ORCID: https://orcid.org/0000-0001-6101-8472)
- Elena Martínez‐Sáez (ORCID: https://orcid.org/0000-0001-6004-5364)
- Esteban Ballestar (ORCID: https://orcid.org/0000-0002-1400-2440)
Institutions
- Universitat Autònoma de Barcelona (ES)
- Universidade do Porto (PT)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Josep Carreras Leukaemia Research Institute (ES)
- Vall d'Hebron Institut de Recerca (ES)
- Instituto Nacional de Saúde (MZ)
- National Institute of Health Dr. Ricardo Jorge (PT)
- East China Normal University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-01-16
- DOI
- https://doi.org/10.1038/s41467-025-56124-1
- Citations
- 63
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 53.06
Funders
- Centres de Recerca de Catalunya
- European Commission
- Generalitat de Catalunya
- Ministerio de Ciencia e Innovación
- Fundació Institut de Recerca Hospital Universitari Vall d’Hebron
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
- Fundação para a Ciência e a Tecnologia
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III
- Agencia Estatal de Investigación
- Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto
- Institut de Recerca contra la Leucèmia Josep Carreras