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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代谢转换和上皮-间充质过渡共同调节多能性。

从氧化磷酸化到糖酵解（OGS）的新陈代谢转换和上皮-间质转化（EMT）都在早期阶段促进细胞重编程。但是，它们的联系尚未阐明。在这里，当在小鼠重编程期间使用化学成分确定的培养基诱导早期EMT时，同时也观察到了促进的OGS。进一步的研究表明，这两个事件通过转录激活形成了一个正反馈环，协同上调了表观遗传因子，例如Bmi1，Ctcf，Ezh2，Kdm2b和Wdr5，并在早期加速了多能性诱导。但是，在后期，通过过度诱导糖酵解并防止必要的间充质-上皮转化，这两个事件使细胞陷入了处于纯态和启动态之间的新的多能状态，并阻止了向纯态的进一步重编程。此外，处于新状态的多能干细胞与来自E4.5和E5.5胚胎的上皮细胞高度相似，并且具有与先前报道的上皮细胞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空合作应该扩展我们对相关领域的理解。