Mechanical control of stem cell differentiation

Abstract

Stem cells interrogate numerous microenvironmental cues, including soluble factors, adhesive contexts, and mechanical signals, in order to mount physiologically relevant differentiation responses. While much is known about how soluble factors and adhesion receptors regulate differential gene expression, the molecular basis for how mechanical signaling controls gene transcription and differentiation programs is only now coming into focus. In this review, we discuss the types of mechanical forces that stem cells experience, and the evidence that applied and cell generated forces regulate stem cell differentiation in vivo and in vitro. In order to understand the mechanistic basis for mechanically-induced differentiation, we explore how mechanical forces are transduced into biochemical signals, that can in turn regulate and synergize with signaling cascades induced by other stimuli. Specifically, we emphasize how applied mechanical forces target the activity and expression or transcription factors and chromatin remodeling enzymes directly involved in gene expression. Furthermore, we highlight recent progress demonstrating that cell-generated forces (intracellular tension) can promote stem cell differentiation in the absence of or in spite of orthogonal signals from soluble factors. Together these findings define an emerging picture of how mechanical forces trigger stem cell differentiation to a specific lineage in complex microenvironments where inducers for multiple cell types are present.