TY - JOUR 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 DO - 10.26508/lsa.202201467 VL - 5 IS - 10 SP - e202201467 AU - Jeesan Lee AU - Oscar David Villarreal AU - Yu Chang Wang AU - Jiannis Ragoussis AU - Serge Rivest AU - David Gosselin AU - Stéphane Richard Y1 - 2022/10/01 UR - https://www.life-science-alliance.org/content/5/10/e202201467.abstract N2 - 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. ER -