The intrahepatic bile duct (IHBD) network is hierarchical in structure with smaller, peripheral “ductules” draining into larger “ducts” that eventually exit the liver. Despite proposed models from histological and genetic studies, mechanisms differentiating local “duct” or “ductule” hierarchies and driving the global IHBD architecture are poorly understood.
Using mice with the conditional knockout of Sox9 in developing liver (Sox9cKO), single cell sequencing identified gene-expression defects in ductule-like biliary epithelial cells (BECs). Other defects leading to incomplete development of ductule architecture were identified. Sox9cKO biliary organoids were then used to identify an important regulatory gene for the development of adult IHBD morphology and BEC maturation.
