Axin2+ Peribiliary Glands in the Periampullary Region Generate Biliary Epithelial Stem Cells That Give Rise to Ampullary Carcinoma

Background & AimsPeribiliary glands (PBGs), clusters of epithelial cells residing in the submucosal compartment extrahepatic bile ducts, have been suggested as biliary stem/progenitor cell niche; however, evidence to support this claim is limited because a lack PBG-specific markers. We therefore sought identify markers investigate potential role PBGs niches, well an origin cancer.MethodsWe examined expression pattern Wnt target gene Axin2 ducts. then applied lineage tracing whether Axin2-expressing from contribute regeneration and carcinogenesis using Axin2-CreERT mice.ResultsWnt signaling activation, marked by Axin2, was located periampullary region. Lineage showed that PBG are capable self-renewal supplying new (BECs) luminal surface. Additionally, mature ductal marker CK19 were mutually exclusive region, fate CK19+ surface BECs gradual replacement CK19– cells, further supporting continuous replenishment also found signal enhancer R-spondin3 secreted Myh11-expressing stromal corresponding human sphincter Oddi, maintained signal–activating niche. Notably, introduction PTEN deletion into Axin2+ but not BECs, induced ampullary carcinoma whose development suppressed inhibitor.ConclusionA specific population receiving Wnt-activating functions cellular carcinoma. Peribiliary cancer. mice. inhibitor. A