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Role of reprogramming factors in transdifferentiation of hepatocytes to biliary epithelial cells

Transdifferentiation of liver epithelial cells (hepatocytes and biliary cells) into each other provides a rescue mechanism in liver disease under situations where either cell compartment fails to regenerate by itself. The mechanisms underlying such transdifferentiation of terminally differentiated epithelial are not known. Recently we reported that adult rat liver expresses reprogramming factors Oct3/4, Nanog, and KLF4, and their expression is important for hepatocyte proliferation and liver regeneration. To test if reprogramming factors play a role in transdifferentiation of hepatocytes to BECs, we used the hepatocyte organoid cultures. In this system, primary hepatocytes when plated on collagen coated roller bottles and cultured in presence of HGF, EGF, and dexamethasone, transdifferentiate to form BECs between 6–8 days in culture. When we looked at the expression of reprogramming factors in this system, we found that Oct3/4, Nanog, and Klf4 are upregulated at day 6 in this system as assessed by mRNA levels suggesting the possible involvement of reprogramming factors in transdifferentiation. Further analysis of protein levels by Western blot, immunohistochemical staining, and intervention studies by blocking reprogramming factors are in progress to elucidate the role of reprogramming factors in transdifferentiation.