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Schematic of experiments by McGinn et al on oesophageal epithelium

A biomechanical switch regulates the transition towards homeostasis in oesophageal epithelium

McGinn J et al. (2021) Nature Cell Biology DOI: 10.1038/s41556-021-00679-w.

In an interdisciplinary collaboration with the Alcolea lab at the Wellcome-MRC Cambridge Stem Cell Institute, the Simons lab shows that physiological stretching in the oesophagus during mouse postnatal development leads to a re-balancing between epithelial stem cell proliferation and differentiationenabling homeostasis to be reached in the adult animal.


Abstract from the paper

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 with which 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 bright Krüppel-like factor 4 (KLF4) committed basal population, which balances cell proliferation and marks the transition towards homeostasis in a yes-associated protein (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.



Read more about research in the Simons lab.

Watch Ben Simons describe his research on YouTube.


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Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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