近日，西班牙欧洲分子生物学实验室教授Vikas Trivedi及其研究组的研究显示，糖酵解活性通过调节Nodal和Wnt信号传导来指导胚层比例。这一研究成果发表在2025年4月16日出版的国际学术期刊《细胞—干细胞》上。

研究小组证明了糖酵解活性在调节中胚层和内胚层规范的信号通路中的指导作用。利用基于多主题胚胎干细胞（mESC）的体外原肠胚形成模型，该课题组研究人员发现糖酵解抑制以牺牲中胚层和内胚层细胞系为代价增加外胚层细胞的命运。课题组研究人员证明这种关系是剂量依赖的，通过外源葡萄糖水平实现胚层比例的代谢控制。该课题组研究人员进一步表明，糖酵解作为Nodal和Wnt信号的上游调节剂，其对细胞命运规范的影响可以与其对生长的影响分离。最后，研究人员证实了他们在人类原肠胚模型上的发现的普遍性。他们的工作强调了信号通路对代谢条件的依赖性，并为细胞命运决策的营养调节提供了机制见解。

据了解，代谢途径可以影响细胞命运的决定，但它们在胚胎发育过程中的调节作用仍然知之甚少。

附：英文原文

Title: Glycolytic activity instructs germ layer proportions through regulation of Nodal and Wnt signaling

Author: Kristina S. Stapornwongkul, Elisa Hahn, Patryk Poliński, Laura Salamó Palau, Krisztina Arató, LiAng Yao, Kate Williamson, Nicola Gritti, Kerim Anlas, Mireia Osuna Lopez, Kiran R. Patil, Idse Heemskerk, Miki Ebisuya, Vikas Trivedi

Issue&Volume: 2025-04-16

Abstract: Metabolic pathways can influence cell fate decisions, yet their regulative role during embryonic development remains poorly understood. Here, we demonstrate an instructive role of glycolytic activity in regulating signaling pathways involved in mesoderm and endoderm specification. Using a mouse embryonic stem cell (mESC)-based in vitro model for gastrulation, we found that glycolysis inhibition increases ectodermal cell fates at the expense of mesodermal and endodermal lineages. We demonstrate that this relationship is dose dependent, enabling metabolic control of germ layer proportions through exogenous glucose levels. We further show that glycolysis acts as an upstream regulator of Nodal and Wnt signaling and that its influence on cell fate specification can be decoupled from its effects on growth. Finally, we confirm the generality of our findings using a human gastrulation model. Our work underscores the dependence of signaling pathways on metabolic conditions and provides mechanistic insight into the nutritional regulation of cell fate decision-making.

DOI: 10.1016/j.stem.2025.03.011

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00101-8