Functional heterogeneity of the intrahepatic biliary epithelium

The objective of this review article is to discuss the latest findings related to the morphological, functional, and proliferative heterogeneity of intrahepatic bile duct epithelial cells (i.e., cholangiocytes) lining the biliary tree. In the first part of the review, after a brief overview of the major functions of cholangiocytes, we will briefly outline the in vivo animal models and the cell systems (i.e., pure subpopulations of small and large cholangiocytes and small and large intrahepatic bile duct units [IBDU]) (Fig. 1), which have been critically important to the elucidation of the functional heterogeneity of cholangiocytes in different portions of the intrahepatic biliary tree. In the second part of the review article, we will discuss the recent findings showing that the intrahepatic biliary tree is heterogeneous with regard to (1) morphology, (2) secretory processes, (3) expression of antigens/ proteins, and (4) proliferative responses to liver injury/ toxins.