Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 469, Issue 3, Pages 424-429Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2015.12.007
Keywords
Human induced pluripotent stem cells; Hepatocyte; Drug metabolism; ATF5; c/EBP alpha; PROX1
Categories
Funding
- Japan Agency for Medical Research and development, AMED [15bk0104005h0003]
- Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research (K-CONNEX)
- Japan Society for the Promotion of Science Fellows
- Human Resource Development Program for Science and Technology, MEXT
- Grants-in-Aid for Scientific Research [13J02987] Funding Source: KAKEN
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Hepatocyte-like cells differentiated from human iPS cells (human iPS-HLCs) are expected to be utilized in drug development and research. However, recent hepatic characterization of human iPS-HLCs showed that these cells resemble fetal hepatocytes rather than adult hepatocytes. Therefore, in this study, we aimed to develop a method to enhance the hepatic function of human iPS-HLCs. Because the gene expression levels of the hepatic transcription factors (activating transcription factor 5 (ATF5), CCAAT/enhancer-binding protein alpha (c/EBP alpha), and prospero homeobox protein 1 (PROX1)) in adult liver were significantly higher than those in human iPS-HLCs and fetal liver, we expected that the hepatic functions of human iPS-HLCs could be enhanced by adenovirus (Ad) vector-mediated ATF5, c/EBPa, and PROX1 transduction. The gene expression levels of cytochrome P450 (CYP) 2C9, 2E1, alpha-1 antitrypsin, transthyretin, Na+/taurocholate cotransporting polypeptide, and uridine diphosphate glucuronosyl transferase 1A1 and protein expression levels of CYP2C9 and CYP2E1 were upregulated by ATF5, c/EBP alpha, and PROX1 transduction. These results suggest that the hepatic functions of the human iPS-HLCs could be enhanced by ATF5, c/EBP alpha, and PROX1 transduction. Our findings would be useful for the hepatic maturation of human iPS-HLCs. (C) 2015 The Authors. Published by Elsevier Inc.
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