Epithelial cells rapidly adapt their behaviour in response to increasing tissue demands. However, the processes that finely control these cell decisions remain largely unknown. The postnatal period covering the transition between early tissue expansion 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. Single-cell RNA sequencing and whole-organ stretching experiments revealed that the mechanical stress experienced by the growing oesophagus triggers the emergence of a basal KLF4 Bright committed population, which balances cell proliferation and marks the transition towards homeostasis in a YAP dependent manner. Our results point to a simple mechanism whereby mechanical changes experienced at the whole tissue level are integrated with those “sensed” at the cellular level to control epithelial cell fate.

To evaluate the status of UK undergraduate urology teaching against the British Association of Urological Surgeons (BAUS) Undergraduate Syllabus for Urology. Secondary objectives included evaluating the type and quantity of teaching provided, the reported performance rate of General Medical Council (GMC)-mandated urological procedures, and the proportion of undergraduates considering urology as a career. Subjects and MethodsThe uroLogical tEAching in bRitish medical schools Nationally (LEARN) study was a national multicentre cross-sectional evaluation. Year 2 to Year 5 medical students and Foundation Year (FY) 1 doctors were invited to complete a survey between 3 October and 20 December 2020, retrospectively assessing the urology teaching received to date. Results are reported according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). ResultsIn all, 7063/8346 (84.6%) responses from all 39 UK medical schools were included; 1127/7063 (16.0%) were from FY1 doctors who reported that the most frequently taught topics in undergraduate training were on urinary tract infection (96.5%), acute kidney injury (95.9%) and haematuria (94.4%). The most infrequently taught topics were male urinary incontinence (59.4%), male infertility (52.4%) and erectile dysfunction (43.8%). Male and female catheterisation on patients as undergraduates was performed by 92.1% and 73.0% of FY1 doctors respectively, and 16.9% had considered a career in urology. Theory-based teaching was mainly prevalent in the early years of medical school, with clinical skills teaching, and

Epithelial cells are highly dynamic and can rapidly adapt their behavior in response to tissue perturbations and increasing tissue demands. However, the processes that finely control these responses and, particularly, the mechanisms that ensure the correct switch to and from normal tissue homeostasis are largely unknown. Here we explore changes in cell behavior happening at the interface between postnatal development and homeostasis in the epithelium of the mouse esophagus, as a physiological model exemplifying a rapid but controlled tissue growth transition. Single cell RNA sequencing and histological analysis of the mouse esophagus reveal significant mechanical changes in the epithelium upon tissue maturation. Organ stretching experiments further indicate that tissue strain caused by the differential growth of the mouse esophagus relative to the entire body promotes the emergence of a defined committed population in the progenitor compartment as homeostasis is established. Our results point to a simple mechanism whereby the mechanical changes experienced at the whole tissue level are integrated with those 'sensed' at the cellular level to control epithelial cell behavior and tissue maintenance.

No abstract