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Oct4 Is Crucial for Transdifferentiation of Hepatocytes to Biliary Epithelial Cells in an in Vitro Organoid Culture Model
Gene Expression
  • Mboya Doffou
  • George Adams
  • William C Bowen
  • Shirish Paranjpe
  • Harish S Parihar
  • Huy Nguyen, Philadelphia College of Osteopathic Medicine
  • George K Michalopoulos
  • Vishakha Bhave, Philadelphia College of Osteopathic Medicine
Document Type
Article
Publication Date
12-6-2017
Abstract

BACKGROUND: Hepatocyte to biliary transdifferentiation has been documented in various models of bile duct injury. In this process, mature hepatocytes transform into mature biliary epithelial cells by acquiring biliary phenotypic markers. Several signaling pathways including PI3 kinase, Notch, Hes1, Sox9, and Hippo are shown to be involved in the process. However, if Oct4 is involved in hepatocyte to biliary transdifferentiation is unknown.

METHODS: We investigated the role of Oct4 in hepatocyte to biliary transdifferentiation utilizing an in vitro organoid culture system as a model of transdifferentiation. Oct4 was inhibited using adenovirus containing Oct4 shRNA. Hepatocyte specific HNF-4α and biliary specific HNF-1β & CK19 expression were assessed to gauge the extent of transdifferentiation.

RESULTS: Oct4 was induced during hepatocyte to biliary transdifferentiation. Oct4 inhibition significantly downregulated the appearance of biliary cells from hepatocytes. This was accompanied by a significant downregulation of signaling pathways including Notch, Sox9, and Hippo.

CONCLUSION: Our findings suggest that Oct4 is crucial for hepatocyte to biliary transdifferentiation and maturation and that it acts upstream of Notch, Sox9, and Hippo signaling in this model. This finding identifies new signaling through Oct4 in plasticity between hepatocytes and biliary epithelial cells, which can be potentially utilized to identify new strategies in chronic biliary diseases.

PubMed ID
29212575
Comments

This article was published in Gene Expression.

The published version is available at https://doi.org/10.3727/105221617X15124876321401.

Copyright © 2018.CC BY-NC 3.0.

Citation Information
Mboya Doffou, George Adams, William C Bowen, Shirish Paranjpe, et al.. "Oct4 Is Crucial for Transdifferentiation of Hepatocytes to Biliary Epithelial Cells in an in Vitro Organoid Culture Model" Gene Expression (2017)
Available at: http://works.bepress.com/vishakha_bhave/17/