Loss of AhR potentiates FoxM1 signaling to enhance self-renewal of colonic stem/progenitor cells

ABSTRACT: The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that senses xenobiotics, diet and gut microbial-derived metabolites, is increasingly recognized as a key regulator of intestinal biology. However, its effects on the function of colonic stem and progenitor cells remain largely unexplored. Here, we observed that inducible deletion of AhR in Lgr5+ stem cells increases the percentage of colonic stem cells and enhances organoid initiating capacity and growth of sorted stem and progenitor cells, while AhR activation has the opposite effect. Moreover, intestinal-specific AhR knockout increases basal stem cell and crypt injury-induced cell proliferation, and promotes colon tumorigenesis in a preclinical colitis-associated tumor model by upregulating FoxM1 signaling. M

SUBMITTER: Huajun Han 

PROVIDER: S-SCDT-EMBOJ-2019-104319 | biostudies-other |

REPOSITORIES: biostudies-other