JAK-STAT Is Restrained by Notch to Control Cell Proliferation of the Drosophila Intestinal Stem Cells

Abstract

The Drosophila midgut epithelium undergoes continuous regeneration that is sustained by multipotent intestinal stem cells (ISCs) underneath. Notch signaling has dual functions to control ISC behavior: it slows down the ISC proliferation and drives the activated ISCs into different differentiation pathways at a dose-dependent manner. Here we identified a molecular mechanism to unite these two contradictory functions. We found JAK-STAT signaling controls ISC proliferation and this ability is negatively regulated by Notch at least through a transcriptional control of the JAK-STAT signaling ligand, unpaired (upd). This study provides insight into how stem cells, under steady conditions, balance the processes of proliferation and differentiation to maintain the stable cellular composition of a healthy tissue.