MicroRNA-7 Specifically Marks the Gut Endocrine Lineage and Controls Progenitor Cell Proliferation Through Egfr

Enteroendocrine cells (EECs) are critical for orchestrating proper responses to nutritional and microbial input. Importantly, EEC progenitors exhibit stem cell potential and contribute to intestinal epithelial proliferation; however, the molecular mechanisms are not well understood. In this study, we first report that miR-7 is a highly specific marker of the EEC lineage and is the most enriched miRNA in Prox1+ EEC progenitors. Next, we show that miR-7 is functionally suppressed in EEC progenitors by pro-proliferative perturbations in mouse and fruit fly. We then demonstrate that miR-7 exerts highly conserved control of intestinal epithelial proliferation and further show that miR-7 regulates the balance between proliferation and differentiation in murine EEC progenitors. Importantly, we also provide the mechanistic insight that miR-7 function is mediated by suppression of Egfr signaling. Overall, this study uncovers a novel role for miRNAs, specifically miR-7, in marking the EEC lineage and controlling the behavior of EEC progenitors.