Artículo
ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain
Autor/es | Stratoulias, Vassilis
Ruiz Laza, Agustín Kanatani, Shigeaki Osman, Ahmed Mohamed Keane, Lily Armengol, Jose A. García Domínguez, Irene Alonso Bellido, Isabel María Venero Recio, José Luis Joseph, Bertrand |
Director | |
Departamento | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular |
Fecha de publicación | 2023 |
Fecha de depósito | 2023-05-25 |
Publicado en |
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Resumen | 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 ... 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. |
Agencias financiadoras | Ministerio de Ciencia e Innovación (MICIN). España European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) Junta de Andalucía Universidad de Sevilla |
Identificador del proyecto | PID2021-124096OB-I00
PID 2019-109569GB-100 BFU2015-68655 P18-RT-1372 FEDER I+D+i-USE US-1264806 |
Cita | Stratoulias, V., Ruiz Laza, A., 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/s41593-023-01326-3. |
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s41593-023-01326-3.pdf | 16.94Mb | [PDF] | Ver/ | |