The metabolic framework of pluripotent stem cells and potential mechanisms of regulation

Abstract

It is becoming increasingly clear that standard measures of embryonic stem cell pluripotency do not necessarily reflect underlying differences in cell physiology. There is an immediate need to expand our knowledge of the basic physiology of pluripotent stem cells and to understand the impact of factors that regulate pluripotent stem-cell expansion, maintenance, and controlled differentiation on cell metabolism. Importantly, the responses of pluripotent stem cells to alterations in culture environment have not been extensively elucidated; this is especially relevant with the recent growth in specialized media formulations available. Coincident with the development and selection of media for pluripotent stem-cell culture, it is imperative to understand the impact each formulation has on the metabolism and physiology of the cells. This is particularly pertinent as cells are being considered for clinical and commercial applications. Consequently, medium selection needs to be made on both functional and physiological grounds. Pluripotent stem cells are characterized by their differentiation potential (pluripotency), defined as their ability to differentiate into cell populations of the three primary lineages, ectoderm, mesoderm, and endoderm, and by their immortality. It is immortality, or the capacity for unlimited self-renewal, which enables continued proliferation of pluripotent stem cells without cellular senescence. Pluripotency is regulated by a complex transcription factor network, centred on OCT4 (POU5F1), NANOG, and SOX2. In addition to these defining features it is becoming apparent that pluripotent stem cells are characterized by a unique physiology. This chapter will focus on the metabolic framework that sustains pluripotent stem cells in culture, potential mechanisms that regulate the physiology of these cells, and the effect of environmental factors on homeostasis in these cells.