Background and Objectives Spermatogonial stem cells (SSCs) are the most primitive cells in spermatogenesis and are the only adult stem cells capable of passing on the genome of a given species to the next generation. SSCs are the only adult stem cells known to exhibit high Oct4 expression and can be induced to self-reprogram into pluripotent cells depending on culture conditions. Epigenetic modulation is well known to be involved in the induction of pluripotency of somatic cells. However, epigenetic modulation in self-reprogramming of SSCs into pluripotent cells has not been studied. Methods and Results In this study, we examined the involvement of epigenetic modulation by assessing whether self-reprogramming of SSCs is enhanced by treatment with epigenetic modulators. We found that second-generation selective class I HDAC inhibitors increased SSC reprogramming efficiency, whereas non-selective HDAC inhibitors had no effect. Conclusions We showed that pluripotent stem cells derived from adult SSCs by treatment with small molecules with epigenetic modulator functions exhibit pluripotency in vitro and in vivo. Our results suggest that the mechanism of SSC reprogramming by epigenetic modulator can be used for important applications in epigenetic reprogramming research.

中文翻译：

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抑制 I 类组蛋白脱乙酰酶可增强精原干细胞自我重编程为多能干细胞。

背景和目的 精原干细胞 (SSCs) 是精子发生过程中最原始的细胞，也是唯一能够将给定物种的基因组传递给下一代的成体干细胞。SSC 是已知的唯一一种表现出高 Oct4 表达的成体干细胞，并且可以根据培养条件诱导自我重编程为多能细胞。众所周知，表观遗传调控参与体细胞多能性的诱导。然而，尚未研究 SSC 自我重编程为多能细胞的表观遗传调节。方法和结果 在这项研究中，我们通过评估表观遗传调节剂治疗是否增强了 SSC 的自我重编程来检查表观遗传调节的参与。我们发现第二代选择性 I 类 HDAC 抑制剂提高了 SSC 重编程效率，而非选择性 HDAC 抑制剂没有效果。结论 我们表明，通过用具有表观遗传调节功能的小分子处理从成人 SSC 衍生的多能干细胞在体外和体内表现出多能性。我们的结果表明表观遗传调节剂对 SSC 重编程的机制可用于表观遗传重编程研究的重要应用。