[en] Molecular 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.
Disciplines :
Neurologie Sciences du vivant: Multidisciplinaire, généralités & autres Biochimie, biophysique & biologie moléculaire Génétique & processus génétiques
Auteur, co-auteur :
Stratoulias, Vassilis ; Institute of Environmental Medicine, Toxicology Unit, Karolinska Institutet, Stockholm, Sweden. vassilis.stratoulias@ki.se ; Neuroscience Center, HiLIFE, University of Helsinki, Helsinki, Finland. vassilis.stratoulias@ki.se
Ruiz, Rocío ; Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC, Universidad de Sevilla, Seville, Spain
Kanatani, Shigeaki ; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
Osman, Ahmed M; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
Keane, Lily; Institute of Environmental Medicine, Toxicology Unit, Karolinska Institutet, Stockholm, Sweden
Armengol, Jose A ; Department of Physiology, Anatomy and Cellular Biology, University of Pablo de Olavide, Seville, Spain
Rodríguez-Moreno, Antonio ; Department of Physiology, Anatomy and Cellular Biology, University of Pablo de Olavide, Seville, Spain
Murgoci, Adriana-Natalia; Institute of Environmental Medicine, Toxicology Unit, Karolinska Institutet, Stockholm, Sweden
García-Domínguez, Irene ; Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC, Universidad de Sevilla, Seville, Spain
Alonso-Bellido, Isabel; Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC, Universidad de Sevilla, Seville, Spain
González Ibáñez, Fernando ; Department of Molecular Medicine, Université Laval, and Axe Neurosciences, Centre de Recherche du CHU de Québec-Université Laval, Laval, Quebec, Canada ; Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
Picard, Katherine ; Department of Molecular Medicine, Université Laval, and Axe Neurosciences, Centre de Recherche du CHU de Québec-Université Laval, Laval, Quebec, Canada ; Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
Vázquez-Cabrera, Guillermo; Institute of Environmental Medicine, Toxicology Unit, Karolinska Institutet, Stockholm, Sweden ; Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC, Universidad de Sevilla, Seville, Spain
Posada-Pérez, Mercedes; Institute of Environmental Medicine, Toxicology Unit, Karolinska Institutet, Stockholm, Sweden ; Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC, Universidad de Sevilla, Seville, Spain
Vernoux, Nathalie; Department of Molecular Medicine, Université Laval, and Axe Neurosciences, Centre de Recherche du CHU de Québec-Université Laval, Laval, Quebec, Canada
Tejera, Dario; Department of Neurodegenerative Diseases and Gerontopsychiatry, University of Bonn, Bonn, Germany
Grabert, Kathleen ; Institute of Environmental Medicine, Toxicology Unit, Karolinska Institutet, Stockholm, Sweden
Cheray, Mathilde ; Institute of Environmental Medicine, Toxicology Unit, Karolinska Institutet, Stockholm, Sweden
González-Rodríguez, Patricia; Institute of Environmental Medicine, Toxicology Unit, Karolinska Institutet, Stockholm, Sweden
Pérez-Villegas, Eva M; Department of Physiology, Anatomy and Cellular Biology, University of Pablo de Olavide, Seville, Spain
Martínez-Gallego, Irene; Department of Physiology, Anatomy and Cellular Biology, University of Pablo de Olavide, Seville, Spain
Lastra-Romero, Alejandro; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
Brodin, David ; Bioinformatics and Expression Analysis Core Facility, Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
Avila-Cariño, Javier; Department of Molecular Biology and Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden
Cao, Yang ; Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden ; Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Airavaara, Mikko ; Neuroscience Center, HiLIFE, University of Helsinki, Helsinki, Finland ; Faculty of Pharmacy, Drug Research Program, University of Helsinki, Helsinki, Finland
Uhlén, Per; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
HENEKA, Michael ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) ; Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA
Tremblay, Marie-Ève ; Department of Molecular Medicine, Université Laval, and Axe Neurosciences, Centre de Recherche du CHU de Québec-Université Laval, Laval, Quebec, Canada ; Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
Blomgren, Klas ; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden ; Department of Paediatric Oncology, Karolinska University Hospital, Stockholm, Sweden
Venero, Jose L ; Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC, Universidad de Sevilla, Seville, Spain
Joseph, Bertrand ; Institute of Environmental Medicine, Toxicology Unit, Karolinska Institutet, Stockholm, Sweden. bertrand.joseph@ki.se
Sigrid Juséliuksen Säätiö Svenska Kulturfonden Academy of Finland Barncancerfonden Spanish Ministerio de Ciencia e Innovación Mexican Council of Science and Technology Wenner-Gren Foundation Cancerfonden Åke Wiberg Stiftelse ERA-NET NEURON Neuroinflammation Fonds de Recherche du Québec - Santé ERA-NET NEURON Neuroinflammation Canada Research Chair (Tier 2) in Neurobiology of Aging and Cognition Swedish governmental grants for researchers working in healthcare Spanish Ministerio de Ciencia e Innovación Spanish Junta de Andalucia Vetenskapsrådet Hjärnfonden Radiumhemmets Forskningsfonder Karolinska Institutet
Subventionnement (détails) :
We 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. We 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. 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). We acknowledge and respect that the University of Victoria is located on the territory of the lək̓ʷəŋən peoples and that the Songhees, Esquimalt and WSÁNEÆ peoples have relationships to this land.We 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. We 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. 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). We acknowledge and respect that the University of Victoria is located on the territory of the lək̓ʷəŋən peoples and that the Songhees, Esquimalt and WSÁNEÆ peoples have relationships to this land.
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