Metabolic and Mechanical Cues Regulating Pluripotent Stem Cell Fate

The ability to shift between metabolic states and to tightly regulate cellular mechanical properties have been described as crucial events in the achievement of correct embryonic development. Indeed, metabolic and mechanical manipulations in vitro have led to the discovery of new methods to control cell fate. As these two modulators are usually studied separately, in this review article, we describe how cellular mechanics and metabolic characteristics regulate embryonic development in vivo and describe the role of these cues in the regulation of pluripotency and differentiation in vitro. We also pinpoint possible connections between metabolism and mechanotransduction, highlighting recent findings in the Yes-associated protein, phosphoinositide 3-kinase, and AMP-activated protein kinase signaling pathways, and how they may be relevant in modulating cell fate in other contexts.