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In recent years, metabolic plasticity of human Pluripotent Stem Cells (hPSCs), including human Embryonic Stem Cells (hESCs) and induced Pluripotent Stem Cells (iPSCs), emerges as an important area to regulate hPSC expansion, differentiation, and the iPSC reprogramming. PSCs have unique energy and biosynthetic requirements and utilize predominantly glucose through glycolysis rather than Oxidative Phosphorylation (OXPHOS) at undifferentiated state. Upon differentiation, the metabolic pathway is observed to shift from glycolysis to OXPHOS. The reverse process is also observed during the reprogramming of somatic cells to iPSCs, where the metabolic pathway shifts from OXPHOS to glycolysis when the cells gain pluripotency. Metabolic pathways of PSCs (e.g. glucose metabolism, mitochondrial function, redox status, etc.) can be regulated by environmental conditions such as oxygen and the biomolecules that act in the intermediate steps of glycolysis and/or OXPHOS. Understanding the metabolic status during different stages of PSC development can benefit various aspects of PSC engineering in expansion, differentiation, and reprogramming.
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