Dynamic adult tracheal plasticity drives stem cell adaptation to changes in intestinal homeostasis.

Abstract

Coordination of stem cell function by local and niche-derived signals is essential to preserve adult tissue homeostasis and organismal health. The vasculature is a prominent component of multiple stem cell niches. However, its role in adult intestinal homeostasis remains largely understudied. Here, we uncover a previously unrecognised crosstalk between adult intestinal stem cells (ISCs) in Drosophila and the vasculature-like tracheal system, which is essential for intestinal regeneration. Following damage to the intestinal epithelium, gut-derived reactive oxygen species (ROS) activate tracheal HIF-1 and bidirectional FGF/FGFR signaling, leading to reversible remodelling of gut-associated terminal tracheal cells and ISC proliferation following damage. Unexpectedly, ROS-induced adult tracheal plasticity involves downregulation of the tracheal specification factor trachealess (trh) and upregulation of IGF2 mRNA-binding protein (IGF2BP2/Imp). Our results reveal a novel intestine/vasculature interorgan communication program, which is essential to adapt stem cells response to the proliferative demands of the intestinal epithelium.