Shimada Ryuki, Koike Hiroko, Hirano Takamasa, Kato Yuzuru, Saga Yumiko
Department of Genetics, SOKENDAI, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
Mammalian Development Laboratory, Department of Gene Function and Phenomics, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
iScience. 2021 Jul 22;24(8):102890. doi: 10.1016/j.isci.2021.102890. eCollection 2021 Aug 20.
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.
在小鼠生殖细胞发育过程中，雄性生殖细胞进入有丝分裂停滞的G0期，这是性别二态性分化的初始步骤。雄性特异性RNA结合蛋白NANOS2在抑制生殖细胞的细胞周期中起关键作用。然而，NANOS2调节细胞周期的详细机制仍不清楚。利用单细胞RNA测序（scRNA-seq），我们提取了野生型和敲除型睾丸中每个生殖细胞的细胞周期状态，并揭示其表达始于有丝分裂细胞并诱导有丝分裂停滞。我们鉴定出mTORC1的一个调节因子以及作为NANOS2的可能靶标。我们提出，细胞周期的抑制是NANOS2的主要功能，并且它是通过转录后抑制以抑制mTORC1活性来介导的。
