Epithelial cell plasticity in metazoans: Evolutionary insights into roles and mechanisms

Epithelial tissues function as multicellular communities that preserve tissue integrity while adapting to diverse environmental stresses by altering cell behaviors. A striking manifestation of such adaptability is cell plasticity, the ability of differentiated cells to revert to stem-like states or adopt alternative fates. Once considered rare and confined to highly regenerative species, cell plasticity is now recognized across the metazoan tree. In early-branching animals such as sponges and cnidarians, transdifferentiation and dedifferentiation are integral to life-cycle transitions and regeneration, whereas in more complex organisms, these processes typically emerge under stress, including stem cell loss or environmental perturbations. Here, we examine epithelial cell plasticity through evolutionary, cellular, and molecular perspectives. Focusing on the intestinal epithelium, we explore findings from mammalian and Drosophila models showing that progenitors and even terminally differentiated cells can dedifferentiate in response to external stimuli that disrupt homeostasis, such as pathogen infection and nutrient fluctuations. We further discuss conserved mechanisms involving intercellular signaling (e.g., Notch, EGFR, and JAK-STAT) and chromatin states primed for reprogramming, modulated by metabolic cues. Together, these insights position cell plasticity as an ancient environmental adaptation strategy, shaped by conserved molecular toolkits and refined by species- and cell lineage-specific innovations.