Cell fate conversion: direct induction of hepatocyte-like cells from fibroblasts

J Cell Biochem. 2013 Feb;114(2):256-65. doi: 10.1002/jcb.24380.

Abstract

One of the essential features of stem cells is their cellular plasticity to differentiate into daughter cells with defined functions. Recently, induction of pluripotent stem cells from somatic cells by defined transcription factors led to the focus on cellular plasticity of terminally differentiated cells. This approach is adopted by other studies to demonstrate the cell fate conversion between different lineages of terminally differentiated cells. We and others showed that induced hepatocyte-like (iHep) cells are directly converted from mouse fibroblasts by overexpression of liver-enriched transcription factors. iHep cells as well as pluripotent stem cell- or mesenchymal stem cell-derived hepatocyte-like cells provide potential cell sources for disease modeling, transplantation, and tissue engineering independent of donor organs. Here, we review the latest advances in generating hepatocyte-like cells and summarize general criteria for evaluating these cells. In addition, we propose a possible role of the p19(Arf) /p53 pathway in cell fate maintenance, which apparently limits the formation of induced pluripotent stem (iPS) cells and iHep cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Lineage
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Fibroblasts* / cytology
  • Fibroblasts* / metabolism
  • Hepatocytes* / cytology
  • Hepatocytes* / metabolism
  • Humans
  • Induced Pluripotent Stem Cells* / cytology
  • Induced Pluripotent Stem Cells* / metabolism
  • Mice
  • Pluripotent Stem Cells / cytology
  • Signal Transduction
  • Transcription Factors / pharmacology
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Cdkn2a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p16
  • Transcription Factors
  • Tumor Suppressor Protein p53