Cellular crosstalk mediated by TGF-β drives epithelial-mesenchymal transition in patient-derived multi-compartment biliary organoids.

ABSTRACT: Deficiencies in the development of epithelial structures and delays in cellular maturation can increase the susceptibility of neonates to disease early in life. To investigate human biliary development and its vulnerability to biliary atresia, a severe pediatric cholangiopathy, we engineered multi-compartment biliary organoids (MBOs) from co-cultures of human liver-derived epithelial organoid cells with human endothelial and mesenchymal cells. MBOs derived from normal livers effectively replicated the epithelial structure of the bile duct epithelium and peribiliary glands (PBGs). Conversely, MBOs from diseased livers exhibited defective epithelial layers, a significant epithelial-mesenchymal transition (EMT), and an activation of the TGF-β/Activin-SMAD2/3 signaling, primarily due to interm

SUBMITTER: Ayabe H 

PROVIDER: S-EPMC12271497 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature