Epithelial cell fate transitions: development meets homeostasis - María P. Alcolea, PhD - Cambridge Stem Cell Institute - Jeffrey Cheah Biomedical Centre - University of Cambridge

Epithelial cells are highly dynamic and can rapidly adapt their behaviour in response to increasing tissue demands. However, the processes that finely control cell fate decisions remain largely unknown. The postnatal period covering the transition between the rapid growth of a tissue after birth and the establishment of adult homeostasis provides a convenient model to explore this question. Here, we demonstrate that the onset of homeostasis in the epithelium of the mouse oesophagus is guided by the progressive build-up of mechanical strain at the organ level. Whole-organ stretching experiments demonstrate that physiological levels of mechanical stress promote the emergence of an early committed basal population, in a YAP dependent manner. This balances cell behaviour and marks the transition towards adult homeostasis. Our observations point to a simple model whereby the mechanical changes experienced at the whole tissue level are integrated with those “sensed” at the cellular level to control epithelial cell behaviour and tissue maintenance.