Data from: Rewiring of embryonic glucose metabolism via suppression of pfk-1/aldolase during mouse chorioallantoic branching

Adapting the energy metabolism state to changing bioenergetic demands is essential for mammalian development accompanying massive cell proliferation and cell differentiation. However, it remains unclear how developing embryos meet the changing bioenergetic demands during the chorioallantoic branching (CB) stage when the maternal-fetal exchange of gases and nutrients is promoted. In this study, using metabolome analysis with mass-labeled glucose, we found that developing embryos redirected glucose carbon flow into the pentose phosphate pathway (PPP) via suppression of the key glycolytic enzymes PFK-1 and aldolase during CB. Concomitantly, embryos had increases in lactate pool size and in the fractional contribution of glycolysis to lactate biosynthesis. Imaging mass spectrometry (IMS) visualized lactate-rich tissues, such as the dorsal or posterior neural tube, somites, and head mesenchyme. Furthermore, we found that the heterochronic gene Lin28a could act as a regulator of the metabolic changes observed during CB. Perturbation of glucose metabolism rewiring by suppressing Lin28a downregulation resulted in perinatal lethality. Thus, our work demonstrates that developing embryos rewire glucose metabolism following CB for normal development.将能量代谢状态适配动态变化的生物能量需求，对于伴随大规模细胞增殖与细胞分化的哺乳动物发育进程而言至关重要。然而，在促进母胎气体与营养物质交换的尿囊绒膜分支（chorioallantoic branching, CB）阶段，发育胚胎如何应对动态变化的生物能量需求，目前仍无定论。本研究借助同位素标记葡萄糖（mass-labeled glucose）的代谢组学分析手段，发现发育胚胎在CB阶段可通过抑制关键糖酵解酶——磷酸果糖激酶-1（phosphofructokinase-1, PFK-1）与醛缩酶（aldolase）的活性，将葡萄糖碳流重定向至磷酸戊糖途径（pentose phosphate pathway, PPP）。与此同时，胚胎的乳酸池容量以及糖酵解对乳酸生物合成的相对贡献占比均显著升高。成像质谱（imaging mass spectrometry, IMS）可实现富含乳酸组织的可视化成像，例如背侧神经管、后神经管、体节以及头部间充质。此外，本研究证实异时基因（heterochronic gene）Lin28a可作为CB阶段代谢变化的调控因子。若通过抑制Lin28a的下调来干扰葡萄糖代谢重编程，则会导致胚胎围产期致死。综上，本研究证明发育胚胎在CB阶段后会对葡萄糖代谢进行重编程，以保障正常发育进程。