Pluripotent stem cells are thought of as a surrogate of early developmental stages that sustain the capacity to generate all cell types in the body, thereby constituting an invaluable tool to address the mechanisms underlying cellular plasticity. In the mouse, cells resembling totipotent 2-cell-stage embryos (2-cell-like cells) arise at a very low frequency in embryonic stem cell (ESC) cultures. However, the extent to which these early-embryonic-like cells recapitulate the molecular features of the early embryo is unclear. Here, we have undertaken a characterization of some of the metabolic features of early-embryonic-like cells in culture. Our data indicate that early-embryonic-like cells exhibit decreased glycolytic and respiratory activity, lower levels of reactive oxygen species and increased glucose uptake, suggesting a shift of the metabolic programme during 2-cell-like cell reprogramming. Accordingly, we find that 2-cell-like cells can be induced by defined metabolites. Thus, in addition to their transcriptional and chromatin features, 2-cell-like cells recapitulate some of the metabolic features of their in vivo counterpart. Altogether, our work underscores a distinct metabolic state of early-embryonic-like cells and identifies compounds that can induce their emergence in vitro.

中文翻译：

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在 2 细胞样细胞出现期间会出现一种独特的代谢状态。


多能干细胞被认为是早期发育阶段的替代物，能够维持在体内生成所有细胞类型的能力，从而构成解决细胞可塑性机制的宝贵工具。在小鼠中，类似于全能 2 细胞阶段胚胎（2 细胞样细胞）的细胞在胚胎干细胞 (ESC) 培养物中出现的频率非常低。然而，这些早期胚胎样细胞在多大程度上再现了早期胚胎的分子特征尚不清楚。在这里，我们对培养物中早期胚胎样细胞的一些代谢特征进行了表征。我们的数据表明，早期胚胎样细胞表现出糖酵解和呼吸活性降低、活性氧水平降低和葡萄糖摄取增加，这表明2细胞样细胞重编程期间代谢程序发生了变化。因此，我们发现特定的代谢物可以诱导 2 细胞样细胞。因此，除了转录和染色质特征外，2 细胞样细胞还概括了其体内对应细胞的一些代谢特征。总而言之，我们的工作强调了早期胚胎样细胞的独特代谢状态，并确定了可以在体外诱导其出现的化合物。