Gut Epithelial Inositol Polyphosphate Multikinase Alleviates Experimental Colitis via Governing Tuft Cell Homeostasis
Seung Eun Park, Dongeun Lee, Jae Woong Jeong, Su‐Hyung Lee, Seung Ju Park, Jaeseung Ryu, Se Kyu Oh, Hanseul Yang, Sungsoon Fang, Seyun Kim
Abstract
BACKGROUND & AIMS: Inositol polyphosphate multikinase (IPMK), an essential enzyme for inositol phosphate metabolism, has been known to mediate major biological events such as growth. Recent studies have identified single-nucleotide polymorphisms in the IPMK gene associated with inflammatory bowel disease predisposition. Therefore, we aimed to investigate the functional significance of IPMK in gut epithelium. METHODS: ) mice, and assessed their vulnerability against dextran sulfate sodium-induced experimental colitis. Both bulk and single-cell RNA sequencing were performed to analyze IPMK-deficient colonic epithelial cells and colonic tuft cells. RESULTS: mice, while neuronal-related cells were relatively decreased. CONCLUSIONS: mice are more prone to colitis. Thus, intestinal epithelial IPMK is a critical regulator of colonic integrity and tissue regeneration by determining tuft cell homeostasis and affecting cholinergic output.