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PRMT1 is required for the generation of MHC-associated microglia and remyelination in the central nervous system.
- Source :
-
Life science alliance [Life Sci Alliance] 2022 Jun 15; Vol. 5 (10). Date of Electronic Publication: 2022 Jun 15 (Print Publication: 2022). - Publication Year :
- 2022
-
Abstract
- 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.<br /> (© 2022 Lee et al.)
Details
- Language :
- English
- ISSN :
- 2575-1077
- Volume :
- 5
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Life science alliance
- Publication Type :
- Academic Journal
- Accession number :
- 35705491
- Full Text :
- https://doi.org/10.26508/lsa.202201467