Evidence of cell-fate conversion from hepatocytes to cholangiocytes in the injured liver: in-vivo genetic lineage-tracing approaches

Curr Opin Gastroenterol. 2015 May;31(3):247-51. doi: 10.1097/MOG.0000000000000172.

Abstract

Purpose of review: Recently, it has been suggested that hepatocytes can potentially convert their fate into that of cholangiocytes when the liver receives an injury. This review concisely summarizes these new findings, especially those obtained in studies using cell-lineage tracing methods.

Recent findings: Recent advances in technologies using mutant mice with a tamoxifen-inducible Cre/loxP system have allowed heritable labeling of a particular type of cell and enabled us to follow the fate of their progeny. This is generally known as 'genetic lineage-tracing', and has been applied in various studies that require tracking of the fate of cells in living mice. Previous studies using these methods have revealed that hepatocytes themselves can give rise to cholangiocytes through Notch-mediated cell-fate conversion from hepatocytes to cholangiocytes in injured liver tissue and at the onset of liver cancer.

Summary: Intensive studies using in-vivo genetic lineage-tracing approaches have provided new insights into the nature of cellular identity and plasticity in the liver, which will contribute to the development of new therapeutic strategies for liver diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Bile Ducts, Intrahepatic / metabolism*
  • Biomarkers
  • Cell Differentiation
  • Cell Lineage
  • Disease Models, Animal
  • Hepatocytes / metabolism*
  • Humans
  • Liver / injuries
  • Liver / pathology*
  • Liver Failure, Acute / pathology*
  • Liver Regeneration
  • Mice, Inbred C57BL
  • Rats
  • Receptors, Notch / metabolism*
  • Signal Transduction

Substances

  • Biomarkers
  • Receptors, Notch