News Releases & Research Results A molecular mechanism underlying the induction of direct hepatic reprogramming: Discovery of a novel mechanism of action of transcription factors

The results of the collaborative study conducted by Professor Atsushi Suzuki and Assistant Professor Kenichi Horisawa of the Medical Institute of Bioregulation, Kyushu University, Professor Yasuyuki Ohkawa of the same institute, Professor Masao Nagasaki of Kyoto University, and Researcher Kazuko Ueno of the National Center for Global Health and Medicine, and others.

• The molecular mechanism underlying the regulation of direct reprogramming (cell-fate conversion) from fibroblasts into hepatocytes was successfully elucidated.
• More specifically, fibroblasts were successfully converted into iHep cells, which have hepatocyte properties, by introducing two transcription factors into the fibroblasts extracted from mouse skin. In addition, an integrated analysis of the changes in gene expression, chromatin status, and epigenomic status during the process of the fibroblasts’ acquisition of hepatocyte fate was performed, and the series of changes in cell status starting from the binding of transcription factors to DNA was successfully elucidated.
• These results may further facilitate elucidation of the mechanism of hepatic cell differentiation and the mechanism through which the disruption of hepatic cell differentiation leads to disease onset.

This program was conducted with the support of the Research Center Network for Realization of Regenerative Medicine and the Practical Research Project for Rare/Intractable Diseases by AMED.

The results of this study were published online in Molecular Cell, an American scientific journal, on August 5.

Horisawa K., et al. The dynamics of transcriptional activation by hepatic reprogramming factors Molecular Cell
DOI：10.1016/j.molcel.2020.07.012