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

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...

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Autores principales: Stratoulias, Vassilis, Ruiz, Rocío, Kanatani, Shigeaki, Osman, Ahmed M., Keane, Lily, Armengol, Jose A., Rodríguez-Moreno, Antonio, Murgoci, Adriana-Natalia, García-Domínguez, Irene, Alonso-Bellido, Isabel, González Ibáñez, Fernando, Picard, Katherine, Vázquez-Cabrera, Guillermo, Posada-Pérez, Mercedes, Vernoux, Nathalie, Tejera, Dario, Grabert, Kathleen, Cheray, Mathilde, González-Rodríguez, Patricia, Pérez-Villegas, Eva M., Martínez-Gallego, Irene, Lastra-Romero, Alejandro, Brodin, David, Avila-Cariño, Javier, Cao, Yang, Airavaara, Mikko, Uhlén, Per, Heneka, Michael T., Tremblay, Marie-Ève, Blomgren, Klas, Venero, Jose L., Joseph, Bertrand
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244174/
https://www.ncbi.nlm.nih.gov/pubmed/37169859
http://dx.doi.org/10.1038/s41593-023-01326-3
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author Stratoulias, Vassilis
Ruiz, Rocío
Kanatani, Shigeaki
Osman, Ahmed M.
Keane, Lily
Armengol, Jose A.
Rodríguez-Moreno, Antonio
Murgoci, Adriana-Natalia
García-Domínguez, Irene
Alonso-Bellido, Isabel
González Ibáñez, Fernando
Picard, Katherine
Vázquez-Cabrera, Guillermo
Posada-Pérez, Mercedes
Vernoux, Nathalie
Tejera, Dario
Grabert, Kathleen
Cheray, Mathilde
González-Rodríguez, Patricia
Pérez-Villegas, Eva M.
Martínez-Gallego, Irene
Lastra-Romero, Alejandro
Brodin, David
Avila-Cariño, Javier
Cao, Yang
Airavaara, Mikko
Uhlén, Per
Heneka, Michael T.
Tremblay, Marie-Ève
Blomgren, Klas
Venero, Jose L.
Joseph, Bertrand
author_facet Stratoulias, Vassilis
Ruiz, Rocío
Kanatani, Shigeaki
Osman, Ahmed M.
Keane, Lily
Armengol, Jose A.
Rodríguez-Moreno, Antonio
Murgoci, Adriana-Natalia
García-Domínguez, Irene
Alonso-Bellido, Isabel
González Ibáñez, Fernando
Picard, Katherine
Vázquez-Cabrera, Guillermo
Posada-Pérez, Mercedes
Vernoux, Nathalie
Tejera, Dario
Grabert, Kathleen
Cheray, Mathilde
González-Rodríguez, Patricia
Pérez-Villegas, Eva M.
Martínez-Gallego, Irene
Lastra-Romero, Alejandro
Brodin, David
Avila-Cariño, Javier
Cao, Yang
Airavaara, Mikko
Uhlén, Per
Heneka, Michael T.
Tremblay, Marie-Ève
Blomgren, Klas
Venero, Jose L.
Joseph, Bertrand
author_sort Stratoulias, Vassilis
collection PubMed
description 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.
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spelling pubmed-102441742023-06-08 ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain Stratoulias, Vassilis Ruiz, Rocío Kanatani, Shigeaki Osman, Ahmed M. Keane, Lily Armengol, Jose A. Rodríguez-Moreno, Antonio Murgoci, Adriana-Natalia García-Domínguez, Irene Alonso-Bellido, Isabel González Ibáñez, Fernando Picard, Katherine Vázquez-Cabrera, Guillermo Posada-Pérez, Mercedes Vernoux, Nathalie Tejera, Dario Grabert, Kathleen Cheray, Mathilde González-Rodríguez, Patricia Pérez-Villegas, Eva M. Martínez-Gallego, Irene Lastra-Romero, Alejandro Brodin, David Avila-Cariño, Javier Cao, Yang Airavaara, Mikko Uhlén, Per Heneka, Michael T. Tremblay, Marie-Ève Blomgren, Klas Venero, Jose L. Joseph, Bertrand Nat Neurosci Article 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. Nature Publishing Group US 2023-05-11 2023 /pmc/articles/PMC10244174/ /pubmed/37169859 http://dx.doi.org/10.1038/s41593-023-01326-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Stratoulias, Vassilis
Ruiz, Rocío
Kanatani, Shigeaki
Osman, Ahmed M.
Keane, Lily
Armengol, Jose A.
Rodríguez-Moreno, Antonio
Murgoci, Adriana-Natalia
García-Domínguez, Irene
Alonso-Bellido, Isabel
González Ibáñez, Fernando
Picard, Katherine
Vázquez-Cabrera, Guillermo
Posada-Pérez, Mercedes
Vernoux, Nathalie
Tejera, Dario
Grabert, Kathleen
Cheray, Mathilde
González-Rodríguez, Patricia
Pérez-Villegas, Eva M.
Martínez-Gallego, Irene
Lastra-Romero, Alejandro
Brodin, David
Avila-Cariño, Javier
Cao, Yang
Airavaara, Mikko
Uhlén, Per
Heneka, Michael T.
Tremblay, Marie-Ève
Blomgren, Klas
Venero, Jose L.
Joseph, Bertrand
ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain
title ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain
title_full ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain
title_fullStr ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain
title_full_unstemmed ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain
title_short ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain
title_sort arg1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244174/
https://www.ncbi.nlm.nih.gov/pubmed/37169859
http://dx.doi.org/10.1038/s41593-023-01326-3
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