The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions
Martins-Ferreira, Ricardo (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Calafell-Segura, Josep (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Leal, Bárbara (Universidade do Porto)
Rodríguez-Ubreva, Javier (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Martinez-Saez, Elena (Universitat Autònoma de Barcelona)
Mereu, Elisabetta (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Pinho E Costa, Paulo (Universidade do Porto)
Laguna, Ariadna (Universitat Autònoma de Barcelona. Institut de Neurociències)
Ballestar, Esteban (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)

Date:	2025
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. The Human Microglia Atlas includes 91,716 brain immune cells covering six neurologic pathologies. It characterizes the signatures of nine populations and describes the expansion of GPNMB-high microglia in Multiple Sclerosis and Alzheimer's Disease.
Grants:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-01213 Instituto de Salud Carlos III PI21/01603 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-01586
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Microglia ; Neuroimmunology ; Neurological disorders ; Data integration
Published in:	Nature communications, Vol. 16 (january 2025) , ISSN 2041-1723

DOI: 10.1038/s41467-025-56124-1
PMID: 39820004

15 p, 3.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles