Fig. 2

Metabolic regulation of hPSC cardiac differentiation and maturation. Undifferentiated hPSCs upregulate glycolysis, glutaminolysis, nucleotide synthesis, one-carbon metabolism, de novo fatty acid synthesis. Cardiac differentiation is enhanced by high glucose, ROS, fatty acylcarnitine, sphingosine-1-phosphate, and lysophosphatidic acid. On the other hand, glucose-derived acetyl-CoA inhibits differentiation. hPSC-CMs are metabolically immature and rely on lactate oxidation and glycolysis. By growing hPSC-CMs with fatty acids in the absence of glucose, hPSC-CMs metabolically mature and activate β oxidation and OXPHOS. Activation of HIF1α inhibits maturation. hPSC-CMs can be purified by utilizing the metabolic features of undifferentiated hPSCs and hPSC-CMs. Glucose- and glutamine-deprived, lactate-supplemented medium can purify hPSCs and eliminate undifferentiated hPSCs and non-cardiomyocytes. OXPHOS, oxidative phosphorylation