The intestinal epithelium maintains tissue homeostasis through continuous self-renewal driven by a population of rapidly cycling stem cells. Upon injury, however, these active stem cells are frequently depleted, necessitating alternative regenerative mechanisms. Increasing evidence suggests that differentiated epithelial cells can regain stem-like properties through cellular plasticity, yet the extracellular cues initiating this process remain incompletely understood. In this study, we investigate the signals that promote dedifferentiation of committed intestinal epithelial cells, focusing on c-KIT–expressing Paneth cells as a model of reserve stem cell activation. Using multiple injury paradigms and genetic models of stem cell loss, we examine how epithelial and stromal compartments coordinate regenerative responses.