Manipulation of metabolism in complex eukaryotic systems to control cellular state

•Metabolites can play decisive roles in control of complex mammalian cell systems.•Metabolism is a crucial effector of stem cell expansion and differentiation.•Endogenous metabolites may have significant anticancer potential.•Cancer stem cells have distinct metabolic characteristics that could be targeted.

The regulation of metabolism is critical to many important cellular processes in higher eukaryotes, and metabolites themselves can have significant regulatory potential in complex phenotypes. Thus, external control of metabolism for both biotechnological and biomedical ends is of great importance. There has been increasing emphasis on using non-genetic approaches for direct, transient control of metabolism and cellular state, with particularly promising applications in stem cell biomanufacturing and cancer. Metabolite-based methods have been used to facilitate expansion of stem cells, to control and prevent their differentiation, and to reprogram cells to a pluripotent state. Similar approaches are also being explored to inhibit the growth of cancer cells.