The mouse embryo undergoes compaction at the 8-cell stage, and its transition to 16 cells generates polarity such that the outer apical cells are trophectoderm (TE) precursors and the inner cell mass (ICM) gives rise to the embryo. Here, we report that this first cell fate specification event is controlled by glucose. Glucose does not fuel mitochondrial ATP generation, and glycolysis is dispensable for blastocyst formation. Furthermore, glucose does not help synthesize amino acids, fatty acids, and nucleobases. Instead, glucose metabolized by the hexosamine biosynthetic pathway (HBP) allows nuclear localization of YAP1. In addition, glucose-dependent nucleotide synthesis by the pentose phosphate pathway (PPP), along with sphingolipid (S1P) signaling, activates mTOR and allows translation of Tfap2c. YAP1, TEAD4, and TFAP2C interact to form a complex that controls TE-specific gene transcription. Glucose signaling has no role in ICM specification, and this process of developmental metabolism specifically controls TE cell fate.

小鼠胚胎在8细胞阶段经历压实，其过渡到16个细胞时会产生极性，从而使外部顶端细胞成为滋养外胚层（TE）前体，而内部细胞团（ICM）产生了胚胎。在这里，我们报告这第一个细胞命运规范事件是由葡萄糖控制的。葡萄糖不促进线粒体ATP的产生，而糖酵解对于形成胚泡是必不可少的。此外，葡萄糖不能帮助合成氨基酸，脂肪酸和核碱基。相反，通过己糖胺生物合成途径（HBP）代谢的葡萄糖允许YAP1的核定位。此外，通过戊糖磷酸途径（PPP）的葡萄糖依赖性核苷酸合成，以及鞘脂（S1P）信号传导，激活mTOR并允许Tfap2c的翻译。YAP1，TEAD4和TFAP2C相互作用形成控制TE特异性基因转录的复合物。葡萄糖信号传导在ICM规范中不起作用，并且这种发育代谢过程特别控制着TE细胞的命运。