RT Journal Article SR Electronic T1 PRMT1 is required for the generation of MHC-associated microglia and remyelination in the central nervous system JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202201467 DO 10.26508/lsa.202201467 VO 5 IS 10 A1 Lee, Jeesan A1 Villarreal, Oscar David A1 Wang, Yu Chang A1 Ragoussis, Jiannis A1 Rivest, Serge A1 Gosselin, David A1 Richard, Stéphane YR 2022 UL https://www.life-science-alliance.org/content/5/10/e202201467.abstract AB 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.