Mechanisms of Cell Plasticity during Injury-Induced Epithelial Reprogramming

Plasticity defines the capacity to change identity in response to stimuli and represents a property intrinsically inherited from embryonic development. The homeostatic epithelial turnover of many organs is guaranteed by plasticity events where stem cell progenitors generate mature differentiated epithelial cells. Plasticity is also a major hallmark of cancer cells, particularly with respect to their ability to escape treatment sensitivity and adapt to the harsh microenvironment.

In the context of tissue injury, modifications of epithelial cell identity represent a fundamental hallmark of damage-induced repair and regenerative processes. Epithelial reprogramming may occur through activation of dedifferentiation programs including fetal reversion and paligenosis, as well as through switches in lineage commitment, such as in transdetermination and transcommitment. Additional mechanisms rely on trans-differentiation processes between different mature epithelial cell types without the involvement of adult stem cells. The activation of all these plastic events supporting epithelial regeneration occurs not only at the phenotypic level but also importantly involves epigenetic control, metabolic rearrangements, and external sensing.

Here we present and discuss the most recent pieces of evidence highlighting the multiple aspects of epithelial cell plasticity involved in the attempt to support repair and regenerative processes. This review will contribute to better define the broad terms of plasticity, especially as it emerged from the latest investigations employing single-cell-based omics, and identify universal and organ-specific mechanisms of injury-induced epithelial reprogramming.