As human pluripotent stem cells (hPSCs) exit pluripotency, they are thought to switch from a glycolytic mode of energy generation to one more dependent on oxidative phosphorylation. Here we show that, although metabolic switching occurs during early mesoderm and endoderm differentiation, high glycolytic flux is maintained and, in fact, essential during early ectoderm specification. The elevated glycolysis observed in hPSCs requires elevated MYC/MYCN activity. Metabolic switching during endodermal and mesodermal differentiation coincides with a reduction in MYC/MYCN and can be reversed by ectopically restoring MYC activity. During early ectodermal differentiation, sustained MYCN activity maintains the transcription of "switch" genes that are rate-limiting for metabolic activity and lineage commitment. Our work, therefore, shows that metabolic switching is lineage-specific and not a required step for exit of pluripotency in hPSCs and identifies MYC and MYCN as developmental regulators that couple metabolism to pluripotency and cell fate determination.

中文翻译：

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MYC通过调节代谢通量来控制人类多能干细胞的命运决定。

随着人类多能干细胞（hPSC）退出多能性，人们认为它们从能量产生的糖酵解模式转换为另一种依赖于氧化磷酸化的模式。在这里，我们表明，尽管代谢转换发生在中胚层和内胚层的早期分化过程中，但高糖酵解通量得以维持，实际上，在早期外胚层规范化过程中是必不可少的。在hPSC中观察到的糖酵解升高需要MYC / MYCN活性升高。内胚层和中胚层分化过程中的代谢转换与MYC / MYCN降低同时发生，可以通过异位恢复MYC活性来逆转。在早期外胚层分化过程中，持续的MYCN活性维持了“开关”基因的转录，而这些基因对于代谢活性和谱系的承接具有速率限制。因此，我们的工作