Shared molecular and cellular programs during regeneration of glandular epithelia

An emerging concept across multiple adult tissues implies that regeneration involves the transient reactivation of developmental programs, rather than exclusively relying on the mobilization of dedicated multipotent adult stem cells. For glandular epithelia such as the ones forming the mammary, salivary, lacrimal, and prostatic glands, revisiting previous literature from this angle points to a convergence toward a similar model of fetal-like reversion in regeneration. Despite differences in embryonic origin, function, and branching morphology, the recurrent involvement of a molecular axis involving YAP, p63, and Notch signaling in the induction and resolution of epithelial plasticity highlights a high degree of pathway conservation. The primary scope of this short review is to critically re-evaluate existing literature under the conceptual framework of fetal-like reversion, aiming to highlight some developmental pathways that are re-utilized during the regeneration of glandular organs and to discuss the broader implications of these shared molecular mechanisms in the context of disease, namely cancer.