SOX9 as a key regulator of tissue remodelling and epithelial cell fate transitions

Epithelial plasticity allows committed cells to bypass rigid differentiation hierarchies, enabling efficient tissue repair through the reactivation of developmental-like programmes. In this review, we focus on the transcription factor SOX9 as a central regulator of epithelial cell fate rewiring. Essential during epithelial development and tissue morphogenesis, SOX9 is dynamically regulated across diverse epithelial tissues following injury, conferring SOX9-expressing cells with an increased ‘stemness’ and repair/regenerative capacity. Emerging evidence suggests that SOX9 may function as a molecular integrator of microenvironmental inputs during tissue perturbations. However, dysregulation or persistent activation of this programme carries inherent risks of fibrosis and malignancy. Future work aimed at understanding how SOX9 integrates biochemical and mechanical cues will be vital for developing strategies to harness the plastic potential of epithelial cells for regenerative medicine and prevent pathologies associated with this plasticity.