PubMed | Advanced Cell Technology, University of Tsukuba, Laboratory of Biochemistry and Molecular Biology, Osaka University and 5 more.
Type: Journal Article | Journal: Proceedings of the National Academy of Sciences of the United States of America | Year: 2014
Interindividual differences in hepatic metabolism, which are mainly due to genetic polymorphism in its gene, have a large influence on individual drug efficacy and adverse reaction. Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells have the potential to predict interindividual differences in drug metabolism capacity and drug response. However, it remains uncertain whether human iPSC-derived HLCs can reproduce the interindividual difference in hepatic metabolism and drug response. We found that cytochrome P450 (CYP) metabolism capacity and drug responsiveness of the primary human hepatocytes (PHH)-iPS-HLCs were highly correlated with those of PHHs, suggesting that the PHH-iPS-HLCs retained donor-specific CYP metabolism capacity and drug responsiveness. We also demonstrated that the interindividual differences, which are due to the diversity of individual SNPs in the CYP gene, could also be reproduced in PHH-iPS-HLCs. We succeeded in establishing, to our knowledge, the first PHH-iPS-HLC panel that reflects the interindividual differences of hepatic drug-metabolizing capacity and drug responsiveness.
Tsutsui T.,Laboratory of Gene Regulation |
Fukasawa R.,Laboratory of Gene Regulation |
Shinmyouzu K.,University of Toyama |
Nakagawa R.,University of Toyama |
And 3 more authors.
Journal of Biological Chemistry | Year: 2013
Background: Two CDK subunits of the Mediator complex play pivotal roles in transcription by a mechanism that has not yet been elucidated. Results: The histone arginine methyltransferase PRMT5 is a Mediator CDK-interacting protein. Conclusion: Mediator-associated PRMT5 symmetrically dimethylates histone H4 arginine 3, and this might cause transcriptional repression. Significance: This work enables further exploration of Mediator functions in transcriptional repression. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.