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PRMT1 is required for the generation of MHC-associated microglia and remyelination in the central nervous system
Remyelination failure in multiple sclerosis leads to progressive demyelination and inflammation, resulting in neurodegeneration and clinical decline. Microglia are innate immune cells that can acquire a regenerative phenotype to promote remyelination, yet little is known about the regulators control...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201232/ https://www.ncbi.nlm.nih.gov/pubmed/35705491 http://dx.doi.org/10.26508/lsa.202201467 |
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author | Lee, Jeesan Villarreal, Oscar David Wang, Yu Chang Ragoussis, Jiannis Rivest, Serge Gosselin, David Richard, Stéphane |
author_facet | Lee, Jeesan Villarreal, Oscar David Wang, Yu Chang Ragoussis, Jiannis Rivest, Serge Gosselin, David Richard, Stéphane |
author_sort | Lee, Jeesan |
collection | PubMed |
description | Remyelination failure in multiple sclerosis leads to progressive demyelination and inflammation, resulting in neurodegeneration and clinical decline. Microglia are innate immune cells that can acquire a regenerative phenotype to promote remyelination, yet little is known about the regulators controlling the regenerative microglia activation. Herein, using a cuprizone (CPZ)-diet induced de- and remyelination mice model, we identify PRMT1 as a driver for MHC-associated microglia population required for remyelination in the central nervous system. The loss of PRMT1, but not PRMT5, in microglia resulted in impairment of the remyelination with a reduction of oligoprogenitor cell number and prolonged microgliosis and astrogliosis. Using single-cell RNA sequencing, we found eight distinct microglial clusters during the CPZ diet, and PRMT1 depleted microglia hindered the formation of the MHC-associated cluster, expressing MHCII and CD11c. Mechanistically, PRMT1-KO microglia displayed reduced the H3K27ac peaks at the promoter regions of the MHC- and IFN-associated genes and further suppressed gene expression during CPZ diet. Overall, our findings demonstrate that PRMT1 is a critical regulator of the MHC- and IFN-associated microglia, necessary for central nervous system remyelination. |
format | Online Article Text |
id | pubmed-9201232 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-92012322022-07-06 PRMT1 is required for the generation of MHC-associated microglia and remyelination in the central nervous system Lee, Jeesan Villarreal, Oscar David Wang, Yu Chang Ragoussis, Jiannis Rivest, Serge Gosselin, David Richard, Stéphane Life Sci Alliance Resources Remyelination failure in multiple sclerosis leads to progressive demyelination and inflammation, resulting in neurodegeneration and clinical decline. Microglia are innate immune cells that can acquire a regenerative phenotype to promote remyelination, yet little is known about the regulators controlling the regenerative microglia activation. Herein, using a cuprizone (CPZ)-diet induced de- and remyelination mice model, we identify PRMT1 as a driver for MHC-associated microglia population required for remyelination in the central nervous system. The loss of PRMT1, but not PRMT5, in microglia resulted in impairment of the remyelination with a reduction of oligoprogenitor cell number and prolonged microgliosis and astrogliosis. Using single-cell RNA sequencing, we found eight distinct microglial clusters during the CPZ diet, and PRMT1 depleted microglia hindered the formation of the MHC-associated cluster, expressing MHCII and CD11c. Mechanistically, PRMT1-KO microglia displayed reduced the H3K27ac peaks at the promoter regions of the MHC- and IFN-associated genes and further suppressed gene expression during CPZ diet. Overall, our findings demonstrate that PRMT1 is a critical regulator of the MHC- and IFN-associated microglia, necessary for central nervous system remyelination. Life Science Alliance LLC 2022-06-15 /pmc/articles/PMC9201232/ /pubmed/35705491 http://dx.doi.org/10.26508/lsa.202201467 Text en © 2022 Lee et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Resources Lee, Jeesan Villarreal, Oscar David Wang, Yu Chang Ragoussis, Jiannis Rivest, Serge Gosselin, David Richard, Stéphane PRMT1 is required for the generation of MHC-associated microglia and remyelination in the central nervous system |
title | PRMT1 is required for the generation of MHC-associated microglia and remyelination in the central nervous system |
title_full | PRMT1 is required for the generation of MHC-associated microglia and remyelination in the central nervous system |
title_fullStr | PRMT1 is required for the generation of MHC-associated microglia and remyelination in the central nervous system |
title_full_unstemmed | PRMT1 is required for the generation of MHC-associated microglia and remyelination in the central nervous system |
title_short | PRMT1 is required for the generation of MHC-associated microglia and remyelination in the central nervous system |
title_sort | prmt1 is required for the generation of mhc-associated microglia and remyelination in the central nervous system |
topic | Resources |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201232/ https://www.ncbi.nlm.nih.gov/pubmed/35705491 http://dx.doi.org/10.26508/lsa.202201467 |
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