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

Metabolic pathways can influence cell fate decisions, but their regulative role during embryonic development remains poorly understood. Here, we demonstrate a crucial role of glycolytic activity in regulating signalling pathways involved in mesoderm and endoderm specification. Using an 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 used single cell RNA sequencing (scRNA-seq) to analyze the mechanistic insight into the nutritional regulation of cell fate decision making. Control gastruloids at 96hpa or treated with indicated chemicals were desegregated and analyzed using scRNAseq.