Journal
LIFE SCIENCE ALLIANCE
Volume 5, Issue 10, Pages -Publisher
LIFE SCIENCE ALLIANCE LLC
DOI: 10.26508/lsa.202201467
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Funding
- Canadian Institute of Health Research [FDN-154303]
- Lady Davis Institute/TD Bank Studentship award
- Mogam Foundation Award
- Fonds de recherche du Quebec Sante (FRQS)
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Failure of remyelination in multiple sclerosis leads to neurodegeneration and clinical decline. Microglia play a role in promoting remyelination, and PRMT1 is identified as a critical regulator for MHC-associated microglia activation.
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.
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