Efficient generation of hepatoblasts from human ES cells and iPS cells by transient overexpression of homeobox gene HEX

Mitsuru Inamura, Kenji Kawabata, Kazuo Takayama, Katsuhisa Tashiro, Fuminori Sakurai, Kazufumi Katayama, Masashi Toyoda, Hidenori Akutsu, Yoshitaka Miyagawa, Hajime Okita, Nobutaka Kiyokawa, Akihiro Umezawa, Takao Hayakawa, Miho K. Furue, Hiroyuki Mizuguchi

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the potential to differentiate into all cell lineages, including hepatocytes, in vitro. Induced hepatocytes have a wide range of potential application in biomedical research, drug discovery, and the treatment of liver disease. However, the existing protocols for hepatic differentiation of PSCs are not very efficient. In this study, we developed an efficient method to induce hepatoblasts, which are progenitors of hepatocytes, from human ESCs and iPSCs by overexpression of the HEX gene, which is a homeotic gene and also essential for hepatic differentiation, using a HEX-expressing adenovirus (Ad) vector under serum/feeder cell-free chemically defined conditions. Ad-HEX-transduced cells expressed α-fetoprotein (AFP) at day 9 and then expressed albumin (ALB) at day 12. Furthermore, the Ad-HEX-transduced cells derived from human iPSCs also produced several cytochrome P450 (CYP) isozymes, and these P450 isozymes were capable of converting the substrates to metabolites and responding to the chemical stimulation. Our differentiation protocol using Ad vector-mediated transient HEX transduction under chemically defined conditions efficiently generates hepatoblasts from human ESCs and iPSCs. Thus, our methods would be useful for not only drug screening but also therapeutic applications.

Original languageEnglish
Pages (from-to)400-407
Number of pages8
JournalMolecular Therapy
Volume19
Issue number2
DOIs
Publication statusPublished - 2011 Feb
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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  • Cite this

    Inamura, M., Kawabata, K., Takayama, K., Tashiro, K., Sakurai, F., Katayama, K., Toyoda, M., Akutsu, H., Miyagawa, Y., Okita, H., Kiyokawa, N., Umezawa, A., Hayakawa, T., Furue, M. K., & Mizuguchi, H. (2011). Efficient generation of hepatoblasts from human ES cells and iPS cells by transient overexpression of homeobox gene HEX. Molecular Therapy, 19(2), 400-407. https://doi.org/10.1038/mt.2010.241