Shaping epithelial tissues by stem cell mechanics in development and cancer

Abstract

Adult stem cells balance self-renewal and differentiation to build, maintain and repair tissues. The role of signalling pathways and transcriptional networks in controlling stem cell function has been extensively studied, but there is increasing appreciation that mechanical forces also have a crucial regulatory role. Mechanical forces, signalling pathways and transcriptional networks must be coordinated across diverse length and timescales to maintain tissue homeostasis and function. Such coordination between stem cells and neighbouring cells dictates when cells divide, migrate and differentiate. Recent advances in measuring and manipulating the mechanical forces that act upon and are produced by stem cells are providing new insights into development and disease. In this Review, we discuss the mechanical forces involved when epithelial stem cells construct their microenvironment and what happens in cancer when stem cell niche mechanics are disrupted or dysregulated. As the skin has evolved to withstand the harsh mechanical pressures from the outside environment, we often use the stem cells of mammalian skin epithelium as a paradigm for adult stem cells shaping their surrounding tissues.