The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions
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 neurodegene...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56124-1 |
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| author | Ricardo Martins-Ferreira Josep Calafell-Segura Bárbara Leal Javier Rodríguez-Ubreva Elena Martínez-Saez Elisabetta Mereu Paulo Pinho E Costa Ariadna Laguna Esteban Ballestar |
| author_facet | Ricardo Martins-Ferreira Josep Calafell-Segura Bárbara Leal Javier Rodríguez-Ubreva Elena Martínez-Saez Elisabetta Mereu Paulo Pinho E Costa Ariadna Laguna Esteban Ballestar |
| author_sort | Ricardo Martins-Ferreira |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2fa40f8370604cd9b1807697f1b34389 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-2fa40f8370604cd9b1807697f1b343892025-01-19T12:30:32ZengNature PortfolioNature Communications2041-17232025-01-0116111510.1038/s41467-025-56124-1The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditionsRicardo Martins-Ferreira0Josep Calafell-Segura1Bárbara Leal2Javier Rodríguez-Ubreva3Elena Martínez-Saez4Elisabetta Mereu5Paulo Pinho E Costa6Ariadna Laguna7Esteban Ballestar8Epigenetics and Immune Disease Group, Josep Carreras Leukaemia Research Institute (IJC), 08916 BadalonaEpigenetics and Immune Disease Group, Josep Carreras Leukaemia Research Institute (IJC), 08916 BadalonaImmunogenetics Laboratory, Molecular Pathology and Immunology Department, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto (ICBAS-UPorto), 4050-313Epigenetics and Immune Disease Group, Josep Carreras Leukaemia Research Institute (IJC), 08916 BadalonaPathology Department, Vall d’Hebron University Hospital, Universitat Autònoma de BarcelonaCellular Systems Genomics Group, Josep Carreras Leukaemia Research Institute (IJC), 08916 BadalonaImmunogenetics Laboratory, Molecular Pathology and Immunology Department, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto (ICBAS-UPorto), 4050-313Neurodegenerative Diseases Research Group, Vall d’Hebron Research Institute (VHIR)-Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)Epigenetics and Immune Disease Group, Josep Carreras Leukaemia Research Institute (IJC), 08916 BadalonaAbstract 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.https://doi.org/10.1038/s41467-025-56124-1 |
| spellingShingle | Ricardo Martins-Ferreira Josep Calafell-Segura Bárbara Leal Javier Rodríguez-Ubreva Elena Martínez-Saez Elisabetta Mereu Paulo Pinho E Costa Ariadna Laguna Esteban Ballestar The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions Nature Communications |
| title | The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions |
| title_full | The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions |
| title_fullStr | The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions |
| title_full_unstemmed | The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions |
| title_short | The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions |
| title_sort | human microglia atlas humica unravels changes in disease associated microglia subsets across neurodegenerative conditions |
| url | https://doi.org/10.1038/s41467-025-56124-1 |
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