ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain

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dc.contributor.authorStratoulias, Vassilis
dc.contributor.authorRuiz, Rocío
dc.contributor.authorKanatani, Shigeaki
dc.contributor.authorOsman, Ahmed M.
dc.contributor.authorKeane, Lily
dc.contributor.authorArmengol, Jose A.
dc.contributor.authorRodríguez-Moreno, Antonio
dc.contributor.authorMurgoci, Adriana-Natalia
dc.contributor.authorGarcía-Domínguez, Irene
dc.contributor.authorAlonso-Bellido, Isabel
dc.contributor.authorGonzález Ibáñez, Fernando
dc.contributor.authorPicard, Katherine
dc.contributor.authorVázquez-Cabrera, Guillermo
dc.contributor.authorPosada-Pérez, Mercedes
dc.contributor.authorVernoux, Nathalie
dc.contributor.authorTejera, Dario
dc.contributor.authorGrabert, Kathleen
dc.contributor.authorCheray, Mathilde
dc.contributor.authorGonzález-Rodríguez, Patricia
dc.contributor.authorTremblay, Marie-Ève
dc.contributor.authorBlomgren, Klas
dc.contributor.authorVenero, Jose L.
dc.contributor.authorJoseph, Bertrand
dc.contributor.authorBrodin, David
dc.contributor.authorCao, Yang
dc.contributor.authorPérez-Villegas, Eva M.
dc.contributor.authorMartínez-Gallego, Irene
dc.contributor.authorLastra-Romero, Alejandro
dc.contributor.authorAvila-Cariño, Javier
dc.contributor.authorAiravaara, Mikko
dc.contributor.authorUhlén, Per
dc.contributor.authorHeneka, Michael T.
dc.date.accessioned2024-01-25T22:25:29Z
dc.date.available2024-01-25T22:25:29Z
dc.date.copyright2023en_US
dc.date.issued2023
dc.descriptionWe would like to thank S. Vazquez and B. Ben-Azu for technical support. We are grateful to P.C. Nahirney for the use of a transmission electron microscope and B. Gowen for technical assistance.en_US
dc.description.abstractMolecular diversity of microglia, the resident immune cells in the CNS, is reported. Whether microglial subsets characterized by the expression of specific proteins constitute subtypes with distinct functions has not been fully elucidated. Here we describe a microglial subtype expressing the enzyme arginase-1 (ARG1; that is, ARG1+ microglia) that is found predominantly in the basal forebrain and ventral striatum during early postnatal mouse development. ARG1+ microglia are enriched in phagocytic inclusions and exhibit a distinct molecular signature, including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3 and Mgl2, compared to ARG1– microglia. Microglial-specific knockdown of Arg1 results in deficient cholinergic innervation and impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, which in turn results in impaired long-term potentiation and cognitive behavioral deficiencies in female mice. Our results expand on microglia diversity and provide insights into microglia subtype-specific functions.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipWe thank the Bioinformatics and Expression Analysis core facility, the Biomedicum Flow Cytometry core facility and the Biomedicum Imaging core facility (with grants from the Strategic Research Area in Neuroscience (StratNeuro) and the Strategic Research Area in Stemc Cells and Regenerative Medicine (StratRegen) supported by the Swedish government) at the Karolinska Institutet for technical support. This research is supported by the Swedish Research Council and the Swedish Brain Foundation (P.U. and B.J.), the Sigrid Jusélius Foundation, the Svenska Kulturfonden and Academy of Finland (33552, V.S.), the Swedish Cancer Foundation (P.U. and B.J.), the Swedish Cancer Society (K.G., P.U. and B.J.), the Karolinska Institutet Foundation (P.G.-R. and B.J.), the Mexican Council of Science and Technology (F.G.I.), the Fonds de recherche du Québec—Santé (K.P.), the Wenner-Gren Foundation (K.G.), the Åke Wibergs Stiftelse (M.C.), the Spanish Ministerio de Ciencia e Innovación/FEDER/UE PID2021-124096OB-I00 (J.L.V.), PID 2019-109569GB-100 (J.A.A.) and BFU2015-68655 (A.R.-M.), the Spanish Junta de Andalucia/FEDER/EU P18-RT-1372 and the Spanish FEDER I+D+i-USE US-1264806 (J.L.V.), the Swedish Childhood Cancer Foundation (K.B., L.K., P.U. and B.J.), the Swedish governmental grants for researchers working in healthcare (K.B.), the Canada Research Chair (Tier 2) in Neurobiology of Aging and Cognition (M.-E.T.), the TracInflam grant from ERA-NET NEURON Neuroinflammation (B.J., M.-E.T. and M.T.H.) and the Academy of Finland (V.S. and M.A.; 309489, 324177).en_US
dc.identifier.citationStratoulias, V., Ruiz, R., Kanatani, S., Osman, A. M., Keane, L., Armengol, J. A., ... Joseph, B. (2023). ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain. Nature Neuroscience, 26, 1008-1020. https://doi.org/10.1038/s41593-023-01326-3en_US
dc.identifier.urihttps://doi.org/10.1038/s41593-023-01326-3
dc.identifier.urihttp://hdl.handle.net/1828/15893
dc.language.isoenen_US
dc.publisherNature Neuroscienceen_US
dc.subject.departmentDivision of Medical Sciences
dc.subject.departmentSchool of Medical Sciences
dc.titleARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brainen_US
dc.typeArticleen_US

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