Chapter 4 Transdifferentiated Hepatocytes in Rat Pancreas

Abstract

Publisher Summary A specialized exocrine pancreatic cell can transform into a different phenotypic cell—the hepatocyte. Although in an adult animal the pancreatic and liver cells are functionally and morphologically different, both organs arise from gut endoderm, thus, sharing a common ancestry. Under proper conditions, repressed liver-specific genes in pancreatic cells are probably derepressed. The way in which such dormant genes are activated is not clear. Although some carcinogens, such as N -methyl- N -nitroso- guanidine, were shown to induce transdifferentiation, the possibility that 4-HAQO-induced genetic alterations may lead to hepatocyte conversion, when subjected to the added stress of copper depletion and repletion, can be excluded in view of the recent observation that a simple copper depletion-repletion regimen can lead to the development of pancreatic hepatocytes. The stability of a differentiated cell could be due to various molecular mechanisms such as DNA methylation, chromatin structure, DNA protein interactions, and DNA rearrangements. Modification of any of these could initiate transdifferentiation. By utilizing a variety of molecular techniques, it is possible to analyze the control mechanisms of tissue-specific gene regulation in pancreatic hepatocytes. Studies with transdifferentiated hepatocytes may be expected to yield considerable new information about the mechanism(s) of cell differentiation and the attendant transcriptional controls.