Journal of Biomedical Engineering and Medical Devices
Open Access

Application of hepatocyte nuclear factor 4γ for establishment of differentiated hepatocytes

International Conference on Pharmaceutical and Biomedical Engineering

October 16-17, 2017 Osaka, Japan

Shota Sasaki, Mizuho Urabe, Tsukasa Maeda, Junko Suzuki, Ryota Irie, Masakiyo Sakaguchi, Frank J Gonzalez and Yusuke Inoue

Gunma University, Japan
Okayama University Graduate School of Medicine, Japan
National Institutes of Health Bethesda, USA

Posters & Accepted Abstracts: J Biomed Eng Med Devic

Abstract :

Hepatocytes play a central role in drug metabolism in liver. In pharmacokinetics tests of new drugs, normal human hepatocytes have been used for evaluation of the drugs. However, supply of the hepatocytes is unstable and it costs expensive. Thus, development of efficient hepatocyte differentiation system using ES and iPS cells has been desired for a long time. Previous studies showed that hepatocyte nuclear factor 4�?± (HNF4�?±), an orphan member of the nuclear receptor superfamily and a master regulator in liver homeostasis, is an essential factor for differentiation of hepatocytes from hepatoblasts and iPS cells. In addition to HNF4�?±, HNF4 family contains other isoform, HNF4�?³ in mammals. Because hepatic HNF4�?³ is hardly detected in normal liver, function of HNF4�?³ remain to be clarified. We found that hepatic expression of HNF4�?³ is markedly up-regulated in liver-specific Hnf4�?±-null mice. Furthermore, two HNF4�?³ variants that have different N-terminal exon, known HNF4�?³1 and novel HNF4�?³2, are also up-regulated in the Hnf4�?±-null mice. Therefore, we investigated whether the HNF4�?³ variants induce transcriptional activity and mRNA expression of the HNF4�?± target genes. As a result, HNF4�?³2, but not HNF4�?³1 was found to have strong transcriptional activity and induce expression of many liver-enriched genes in HCCderived HepG2 cells when compared to HNF4�?±, suggesting that HNF4�?³2 could be a new hepatocyte redifferentiation factor. These findings may contribute to establishment of differentiated hepatocytes using ES and iPS cells and development of HCC therapy by introducing HNF4�?³2. Recent Publications 1.A Moriimoto, Sasaki S, et al. (2017) An HNF4�?±-microRNA-194/192 Signaling Axis Maintains Hepatic Cell Function. J Biol Chem; 292(25): 10574-10585. 2.S Matsuo, Shota Sasaki, et al. (2016) Hepatocyte Nuclear Factor 4�?± Controls Iron Metabolism and Regulates Transferrin Receptor 2 in Mouse Liver. J Biol Chem.; 290(52): 30855-65.

Biography :

Shota Sasaki is currently pursuing Science and Technology Doctoral course in Gunma University. He has published 2 papers in reputed journals.