Mechanical constraints on cell plasticity: insights from the olfactory epithelium

Abstract

The olfactory epithelium (OE) is a unique model to study how mechanical forces and tissue architecture regulate stem cell plasticity. In vertebrate, its lifelong neurogenesis and regenerative capacity depend on horizontal basal cells and globose basal cells, whose plasticity is gated by niche architecture and morphogenetic cues. While molecular pathways in OE development and regeneration are well-characterized, the role of physical forces, from basal niche stiffness to lamellar folding, remains unexplored. This review integrates single-cell analyses, developmental studies, and mechanobiology to propose that the unique structure of the OE (pseudostratified epithelium, spatial compartmentalization) and conserved pathways (YAP, CXCR4, retinoic acid) coordinate plasticity across ontogeny. We discuss how disrupted mechanoregulation might drive olfactory deficits in aging, infection (COVID-19), congenital disorders (Kallmann syndrome), cancer, and outline key questions and processes to decode the mechanobiological rules governing stem cell and progenitor plasticity. A table summarising the tools available at the cellular and tissue levels for manipulating forces and visualising their effects is provided.