Both metabolic switch from oxidative phosphorylation to glycolysis (OGS) and epithelial-mesenchymal transition (EMT) promote cellular reprogramming at early stages. However, their connections have not been elucidated. Here, when a chemically defined medium was used to induce early EMT during mouse reprogramming, a facilitated OGS was also observed at the same time. Additional investigations suggested that the two events formed a positive feedback loop via transcriptional activation, cooperated to upregulate epigenetic factors such as Bmi1, Ctcf, Ezh2, Kdm2b, and Wdr5, and accelerated pluripotency induction at the early stage. However, at late stages, by over-inducing glycolysis and preventing the necessary mesenchymal-epithelial transition, the two events trapped the cells at a new pluripotency state between naïve and primed states and inhibited further reprogramming toward the naïve state. In addition, the pluripotent stem cells at the new state have high similarity to epiblasts from E4.5 and E5.5 embryos, and have distinct characteristics from the previously reported epiblast-like or formative states. Therefore, the time-dependent cooperation between OGS and EMT in regulating pluripotency should extend our understanding of related fields.

中文翻译：

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代谢开关和上皮间质转化共同调节多能性。


从氧化磷酸化到糖酵解（OGS）和上皮间质转化（EMT）的代谢转变都促进早期细胞重编程。然而，他们的联系尚未阐明。在这里，当使用化学成分确定的培养基在小鼠重编程过程中诱导早期 EMT 时，同时还观察到了促进的 OGS。进一步的研究表明，这两个事件通过转录激活形成正反馈环，协同上调Bmi1、Ctcf、Ezh2、Kdm2b和Wdr5等表观遗传因子，并加速早期多能性的诱导。然而，在后期，通过过度诱导糖酵解并阻止必要的间充质-上皮转化，这两个事件将细胞困在幼稚状态和引发状态之间的新的多能状态，并抑制向幼稚状态的进一步重编程。此外，新状态的多能干细胞与E4.5和E5.5胚胎的外胚层具有高度相似性，并且具有与先前报道的外胚层样或形成状态不同的特征。因此，OGS 和 EMT 在调节多能性方面的时间依赖性合作应该扩展我们对相关领域的理解。