Fate tracing of hepatocytes in mouse liver

Sci Rep. 2017 Nov 23;7(1):16108. doi: 10.1038/s41598-017-15973-7.

Abstract

Hepatocytes perform most of the functions of the liver and are considered terminally differentiated cells. Recently, it has been suggested that hepatocytes might have the potential to transdifferentiate or dedifferentiate under physiological or pathological conditions in vivo. Epithelial-mesenchymal transition of hepatocytes in liver fibrosis has also been proposed. However, these findings have not been fully confirmed. In this study, hepatocytes were genetically labelled for cell fate tracing using lacZ via the tamoxifen-induced CreERT/loxP system. After induction with tamoxifen, alb + cells were permanently marked by lacZ expression, and all progeny lacZ + cells were derived from a single source with no interference. We did not observe transdifferentiation or dedifferentiation of hepatocytes into cholangiocytes or hepatic progenitor cells under conditions of liver homeostasis or following a 2/3 partial hepatectomy. Meanwhile, lacZ/OPN-positive cells were observed in livers of 3,5-diethoxycarbonyl-1,4-dihydrocollidine-fed mice, and lacZ/alpha-smooth muscle actin-positive cells were detected in carbon tetrachloride-induced chronic liver injury models. These results suggested that some existing differentiated alb + cells might have the potential of transdifferentiation/dedifferentiation or epithelial-to-mesenchymal transition in vivo in some liver injury models, but the proportion of these alb + cells in liver was very low, and their significance and actual function during the pathological process remains to be elucidated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Tetrachloride / pharmacology
  • Cell Differentiation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects
  • Hepatic Stellate Cells / cytology
  • Hepatic Stellate Cells / drug effects
  • Hepatocytes / cytology*
  • Hepatocytes / drug effects
  • Liver / cytology*
  • Liver / drug effects
  • Liver / metabolism
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / therapy
  • Liver Regeneration / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Tamoxifen / pharmacology

Substances

  • Tamoxifen
  • Carbon Tetrachloride