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

2025-01-16Artigo científico Acesso aberto
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dc.contributor.authorMartins-Ferreira, Ricardo
dc.contributor.authorCalafell-Segura, Josep
dc.contributor.authorLeal, Bárbara
dc.contributor.authorRodríguez-Ubreva, Javier
dc.contributor.authorMartínez-Saez, Elena
dc.contributor.authorMereu, Elisabetta
dc.contributor.authorPinho e Costa, Paulo
dc.contributor.authorLaguna, Ariadna
dc.contributor.authorBallestar, Esteban
dc.date.accessioned2026-02-16T12:33:44Z
dc.date.available2026-02-16T12:33:44Z
dc.date.issued2025-01-16
dc.description.abstractDysregulated 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.eng
dc.description.sponsorshipE.B. is funded by the Spanish Ministry of Science and Innovation (MICINN) [PID2020117212RB-I00; AEI/10.13039/501100011033] and the Catalan Agency for Management of University and Research Grants (AGAUR, 2021 SGR 01213). R.M.-F. was funded by an FCT (Fundação para a Ciência e Tecnologia) fellowship (SFRH/BD/137900/2018). UMIB is funded by FCT Portugal (UIDB/00215/2020 and UIDP/00215/2020), and ITR (LA/P/006/2020). A.L. is funded by Fondo de Investigación Sanitaria-Instituto de Salud Carlos III (Spain)-FEDER (PI21/01603) and MICINN (Ramón y Cajal [RYC2021-032947-I] financed by MCIN/AEI/10.13039/501100011033 and the European Union-NextGenerationEU/PRTR). EM.‘s work in this publication was supported by the Ramón y Cajal fellowship RYC2021-032359-I, funded by the Spanish Ministry of Science, and by the Catalan Agency for Management of University and Research Grants (AGAUR, 2021 SGR 01586).
dc.identifier.citationNat Commun. 2025 Jan 16;16(1):739. doi: 10.1038/s41467-025-56124-1
dc.identifier.doi10.1038/s41467-025-56124-1
dc.identifier.eissn2041-1723
dc.identifier.pmid39820004
dc.identifier.urihttp://hdl.handle.net/10400.18/10941
dc.language.isoeng
dc.peerreviewedyes
dc.publisherNature Research
dc.relationEpigenetic regulation of signalling pathways in MTLE-HS and its impact on epileptogenesis
dc.relationUnit for Multidisciplinary Research in Biomedicine
dc.relationUnit for Multidisciplinary Research in Biomedicine
dc.relation.hasversionhttps://www.nature.com/articles/s41467-025-56124-1
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectMicroglia
dc.subjectNeuroimmunology
dc.subjectNeurological Disorders
dc.subjectData Integration
dc.subjectDoenças Genéticas
dc.titleThe Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditionseng
dc.typejournal article
dcterms.referenceshttps://www.nature.com/articles/s41467-025-56124-1#Sec22
dspace.entity.typePublication
oaire.awardTitleEpigenetic regulation of signalling pathways in MTLE-HS and its impact on epileptogenesis
oaire.awardTitleUnit for Multidisciplinary Research in Biomedicine
oaire.awardTitleUnit for Multidisciplinary Research in Biomedicine
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POR_NORTE/SFRH%2FBD%2F137900%2F2018/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00215%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F00215%2F2020/PT
oaire.citation.issue1
oaire.citation.startPage739
oaire.citation.titleNature Communications
oaire.citation.volume16
oaire.fundingStreamPOR_NORTE
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
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