Biophysical signals controlling cell fate decisions: how do stem cells really feel?

Self-renewal and differentiation are fundamental stem cell fate decisions, which are essential for normal tissue development, homeostasis, and repair. Extracellular signals, including mechanical and biophysical forces, play an important role in directing the behaviour of a variety of stem and progenitor cells, and recent studies have provided new insights into the molecular mechanisms of these responses. While integrin receptors transmit forces from the extracellular matrix to the cell, the actin cytoskeleton and Rho-GTPases, mediate downstream signal transduction. To affect stem cell fate, however, these signalling cascades must ultimately be transduced into specific transcription responses. Serum response factor (SRF) and yes-associated protein (YAP) are two examples of mechano-sensitive transcription factors, which have recently been implicated in epidermal and mesenchymal stem cell differentiation. Significant challenges for future studies will likely include measuring the relevant biophysical forces experienced by cells in vivo and translating the current knowledge into regenerative therapies.