Our understanding of pluripotency remains limited: iPSC generation has only been established for a few model species, pluripotent stem cell lines exhibit inconsistent developmental potential, and germline transmission has only been demonstrated for mice and rats. By swapping structural elements between Sox2 and Sox17, we built a chimeric super-SOX factor, Sox2-17, that enhanced iPSC generation in five tested species: mouse, human, cynomolgus monkey, cow, and pig. A swap of alanine to valine at the interface between Sox2 and Oct4 delivered a gain of function by stabilizing Sox2/Oct4 dimerization on DNA, enabling generation of high-quality OSKM iPSCs capable of supporting the development of healthy all-iPSC mice. Sox2/Oct4 dimerization emerged as the core driver of naive pluripotency with its levels diminished upon priming. Transient overexpression of the SK cocktail (Sox+Klf4) restored the dimerization and boosted the developmental potential of pluripotent stem cells across species, providing a universal method for naive reset in mammals.

中文翻译：

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高度合作的嵌合super-SOX诱导跨物种的幼稚多能性

我们对多能性的理解仍然有限：仅在少数模型物种中建立了 iPSC 生成，多能干细胞系表现出不一致的发育潜力，并且仅在小鼠和大鼠中证明了种系传递。通过交换 Sox2 和 Sox17 之间的结构元件，我们构建了一种嵌合超级 SOX 因子 Sox2-17，它增强了五个测试物种（小鼠、人类、食蟹猴、牛和猪）的 iPSC 生成。在 Sox2 和 Oct4 之间的界面处将丙氨酸交换为缬氨酸，通过稳定 DNA 上的 Sox2/Oct4 二聚化来获得功能，从而能够生成能够支持健康全 iPSC 小鼠发育的高质量 OSKM iPSC。Sox2/Oct4 二聚化成为幼稚多能性的核心驱动因素，其水平在启动后降低。SK 混合物 (Sox+Klf4) 的瞬时过表达恢复了二聚化，并增强了跨物种多能干细胞的发育潜力，为哺乳动物的幼稚重置提供了一种通用方法。