Melatonin Synergizes with Prostaglandin E2 to Enhance YAP-mediated Regenerative Epithelial Cell Emergence During Intestinal Repair

In this study, we explore the role of melatonin, abundantly secreted by enteroendocrine cells (EECs) yet overlooked beyond its circadian regulation, in promoting intestinal regeneration. Our findings demonstrate that melatonin can be integrated into the PGE2-EP4-YAP signaling axis to facilitate injury-responsive reprogramming and RSC induction in the intestinal epithelium both in vitro and in vivo. This work uncovers a novel function of melatonin, opening new therapeutic possibilities in regenerative medicine. Overall design: The scRNAseq profiles were derived from two groups of mouse small intestinal organoids, treated and untreated melatonin using the 10x Genomics platform.