| First Author | Lee J | Year | 2022 |
| Journal | Life Sci Alliance | Volume | 5 |
| Issue | 10 | PubMed ID | 35705491 |
| Mgi Jnum | J:341703 | Mgi Id | MGI:7310997 |
| Doi | 10.26508/lsa.202201467 | Citation | Lee J, et al. (2022) PRMT1 is required for the generation of MHC-associated microglia and remyelination in the central nervous system. Life Sci Alliance 5(10):e202201467 |
| abstractText | 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. |
