PT  - JOURNAL ARTICLE
AU  - Lee, Jeesan
AU  - Villarreal, Oscar David
AU  - Wang, Yu Chang
AU  - Ragoussis, Jiannis
AU  - Rivest, Serge
AU  - Gosselin, David
AU  - Richard, Stéphane
TI  - PRMT1 is required for the generation of MHC-associated microglia and remyelination in the central nervous system
AID  - 10.26508/lsa.202201467
DP  - 2022 Oct 01
TA  - Life Science Alliance
PG  - e202201467
VI  - 5
IP  - 10
4099  - https://www.life-science-alliance.org/content/5/10/e202201467.short
4100  - https://www.life-science-alliance.org/content/5/10/e202201467.full
SO  - Life Sci. Alliance2022 Oct 01; 5
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.