CFTR represses a PDX1 axis to govern pancreatic ductal cell fate.

ABSTRACT: Inflammation, acinar atrophy, and ductal hyperplasia drive pancreatic remodeling in newborn cystic fibrosis (CF) ferrets lacking a functional cystic fibrosis conductance regulator (CFTR) channel. These changes are associated with a transient phase of glucose intolerance that involves islet destruction and subsequent regeneration near hyperplastic ducts. The phenotypic changes in CF ductal epithelium and their impact on islet function are unknown. Using bulk RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), and assay for transposase-accessible chromatin using sequencing (ATAC-seq) on CF ferret models, we demonstrate that ductal CFTR protein constrains PDX1 expression by maintaining PTEN and GSK3β activation. In the absence of CFTR protein, centroacinar cells adopted a bipote

SUBMITTER: Rotti PG 

PROVIDER: S-EPMC11647141 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature