NANOS2 suppresses the cell cycle by repressing mTORC1 activators in embryonic male germ cells.

During murine germ cell development, male germ cells enter the mitotically arrested G0 stage, which is an initial step of sexually dimorphic differentiation. The male-specific RNA-binding protein NANOS2 has a key role in suppressing the cell cycle in germ cells. However, the detailed mechanism of how NANOS2 regulates the cell cycle remains unclear. Using single-cell RNA sequencing (scRNA-seq), we extracted the cell cycle state of each germ cell in wild-type and -KO testes and revealed that expression starts in mitotic cells and induces mitotic arrest. We identified , a regulator of mTORC1, and as possible targets of NANOS2. We propose that repression of the cell cycle is a primary function of NANOS2 and that it is mediated via the suppression of mTORC1 activity through the repression of in a post-transcriptional manner.