Rapid cell-fate conversion of mouse fibroblasts into hepatocyte-like cells  [in Japanese]

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Author(s)

    • Miura Shizuka
    • Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
    • Suzuki Atsushi
    • Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan|Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Saitama, Japan

Abstract

Recent progress in studies on direct cell-fate conversion of differentiated somatic cells into other cell types, which is known as “direct reprogramming”, is expected to lead to innovations in health care. In our previous study, we found that three specific combinations of two transcription factors, comprising Hnf4α plus Foxa1, Foxa2, or Foxa3, were able to induce conversion of mouse fibroblasts into functional hepatocyte-like cells. These induced hepatocyte-like (iHep) cells will be useful for developing regenerative therapies for liver diseases and examining the pharmacological effects of drugs. However, to evaluate the potential utility of iHep cells, the phenomena involved in the direct conversion of fibroblasts into iHep cells should be examined in detail. Thus, in this study, we sequentially analyzed the early stage of fibroblast conversion into iHep cells after infection with retroviruses expressing <I>Hnf4α</I> and <I>Foxa3</I>. Our data demonstrated that the conversion into iHep cells began within 2 days after introduction of the transgenes into fibroblasts, and the number of iHep cells increased gradually as the culture progressed. The rapid cell-fate conversion of fibroblasts into iHep cells and stable expansion of iHep cells are two pieces of evidence suggesting the utility of iHep cells for cell transplantation therapy, bioartificial liver development, and screening of drugs for patients with liver diseases, which require many hepatocytes within a short period of time.

Journal

  • Inflammation and Regeneration

    Inflammation and Regeneration 34(5), 211-216, 2014

    The Japanese Society of Inflammation and Regeneration

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