PRMT5 deficiency enforces the transcriptional and epigenetic programs of Klrg1+CD8+ terminal effector T cells [scRNA-seq]

Protein arginine methyltransferase 5 (PRMT5) participates in symmetric dimethylation of arginine residues of proteins and contributes to a wide range of biological processes. But how PRMT5 affects the transcriptional and epigenetic programs involved in the establishment and maintenance of T cell subsets differentiation and roles in antitumor immunity are still incompletely understood. Here, using the single cell RNA sequencing, CHIP-sequencing and bulk RNA sequencing, we found that mice T cell-specific deletion of PRMT5 had greater effects on CD8+ than CD4+ T cells development, enforcing CD8+ T cells differentiation into Klrg1+ terminal effector cells. Mechanically, T cells deficiency of PRMT5 activated Prdm1 by decreasing H4R3me2s and H3R8me2s deposition on its loci, which promote differentiation of Klrg1+CD8+ T cells. Furthermore, effector CD8+ T cells that transited into memory precursor cells were decreased in PRMT5 deficiency T cells thus caused dramatic CD8+ T cells death. CD3+ T cells were isolated from control (WT) (n=3) and PRMT5 CKO (CRE) (n=3) mice spleens and used for single cell RNA sequencing.