A biomechanical switch regulates the transition towards homeostasis in esophageal epithelium

Abstract

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.

A Scarless Healing Tale: Comparing Homeostasis and Wound Healing of Oral Mucosa With Skin and Oesophagus

“…Furthermore, tissue expansion during growth or in adulthood (for example, ventral skin during pregnancy) also regulates SC division rate and global behaviour. This further supports the notion that SC behaviour is regulated by a combination of molecular and mechanical cues that regulate tissue microenvironment and cell behaviour ( Vining and Mooney, 2017 ; Li et al, 2018 ; Shyer et al, 2018 ; Aragona et al, 2020 ; Biggs et al, 2020 ; Mcginn et al, 2021 ). Importantly, one of the crucial components of the microenvironment surrounding epithelial progenitor cells are fibroblasts.…”

Defining the transcriptional signature of esophageal-to-skin lineage conversion

“…The signature of this cluster was marked by the expression of genes directly associated with hypoxia, wound healing and cancer (Pgf, Adm2, Ero1l; SFig.4B) 34, [69][70][71] . Given that previous in vivo scRNA-seq analysis of adult mouse esophagus did not reveal the presence of a C8 equivalent cluster 38 , these results indicate that the C8 population naturally emerges during the normal re-epithelialization process.…”