Early Pathogenesis of Cystic Fibrosis Gallbladder Disease in a Porcine Model

Hepatobiliary disease causes significant morbidity in people with cystic fibrosis (CF), yet this problem remains understudied. We previously found that newborn CF pigs have microgallbladders with significant luminal obstruction in the absence of infection and inflammation. In this study, we sought to better understand the early pathogenesis of CF pig gallbladder disease. We hypothesized that loss of CFTR would impair gallbladder epithelium anion/liquid secretion and increase mucin production. By single cell RNA sequencing, we identified a single epithelial cell population that co-expressed CFTR, MUC5AC, and MUC5B. By bulk tissue RNA sequencing, there was no significant difference in the epithelial expression of gel-forming mucins between non-CF and CF pig gallbladders. Also, there were minimal transcriptional changes in CF relative to non-CF. Overall design: Total RNA sequencing of cystic fibrosis (CF) and non-CF pig gallbladders. Single cell RNA sequencing of non-CF pig gallbladder.