Mus musculus strain:C57BL/6 Transcriptome or Gene expression

The Aryl hydrocarbon receptor (AhR) in the intestine “senses” AhR-active metabolites/nutrients to promote intestinal health. Since perturbations in stem cell plasticity are believed to represent the earliest step towards colon tumorigenesis, we investigated the role of the AhR with respect to colonic stem cell (CSC) and progenitor cell homeostasis. AhR knockout targeted to Lgr5+ CSCs or the intestinal epithelium enhanced Lgr5+ CSC cell division and progenitor cell stemness potential (organoid initiating capacity), while AhR activation exerted the opposite effect. Consistent with these observations, RNA sequencing data from sorted stem and progenitor cells revealed that AhR knockout increased the expression level of genes involved in cell cycle progression and cell proliferation. In addition, targeted deletion of AhR in the intestine promoted colon tumorigenesis in a preclinical model of colitis-associated cancer. These findings provide new mechanistic insight into how AhR signaling in epithelial cells modulates the dynamics and functionality of CSCs.