posted on 2016-06-09, 00:00authored byLianghui Zhang, Glenn Marsboom, Danielle Glick, Yanmin Zhang, Peter T. Toth, Nicole Jones, Asrar B. Malik, Jalees Rehman
Two defining characteristics of stem cells are their multilineage differentiation potential (multipotency
or pluripotency) and their capacity for self-renewal. Growth factors are well-established regulators
of stem cell differentiation and self renewal, but less is known about the influence of the metabolic state on
stem cell function. Recent studies investigating cellular metabolism during the differentiation of adult stem
cells, human embryonic stem cells (ESCs), and induced pluripotent stem cells have demonstrated that activation
of specific metabolic pathways depends on the type of stem cells as well as the lineage cells are
differentiating into and that these metabolic pathways can influence the differentiation process. However,
some common patterns have emerged, suggesting that undifferentiated stem cells primarily rely on glycolysis
to meet energy demands. Our own data indicate that undifferentiated ESCs not only exhibit a low
mitochondrial membrane potential but also express high levels of the mitochondrial uncoupling protein 2
and of glutamine metabolism regulators when compared with differentiated cells. More importantly, interventions
that target stem cell metabolism are able to either prevent or enhance differentiation. These findings
suggest that the metabolic state of stem cells is not just a marker of their differentiation status but also
plays an active role in regulating stem cell function. Regulatory metabolic pathways in stem cells may thus
serve as important checkpoints that can be modulated to direct the regenerative capacity of stem cells.