Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Dev Cell. 2020 Apr 6;53(1):9-26.e4. doi: 10.1016/j.devcel.2020.02.015. Epub 2020 Mar 19.
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 细胞期经历致密化，其向 16 细胞的转变产生极性，使得外层顶端细胞成为滋养外胚层 (TE) 前体细胞，而内细胞团 (ICM) 则产生胚胎。在这里，我们报告说，这个第一个细胞命运特化事件受葡萄糖控制。葡萄糖不会为线粒体 ATP 生成提供燃料，糖酵解对于囊胚形成是可有可无的。此外，葡萄糖无助于合成氨基酸、脂肪酸和核苷。相反，己糖胺生物合成途径 (HBP) 代谢的葡萄糖允许 YAP1 核定位。此外，戊糖磷酸途径 (PPP) 依赖葡萄糖的核苷酸合成以及神经酰胺 (S1P) 信号转导激活 mTOR 并允许 Tfap2c 的翻译。YAP1、TEAD4 和 TFAP2C 相互作用形成一个复合物，控制 TE 特异性基因转录。葡萄糖信号在 ICM 特化中不起作用，而这种发育代谢过程专门控制 TE 细胞命运。
