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J Pharmacol Sci. 2019 Jun 21. pii: S1347-8613(19)34171-4. doi: 10.1016/j.jphs.2019.06.006. [Epub ahead of print]

Systematic expression analysis of genes related to generation of action potentials in human iPS cell-derived cardiomyocytes.

Author information

1
Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan; Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, 113-0032, Japan.
2
Department of Pharmacology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan; Department of Physiology and Membrane Biology, University of California, Davis, CA, 95616, USA.
3
Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
4
Department of Bio-informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan.
5
Laboratory of Bio-Molecular Dynamics, Department of Collaborative Research, Nara Medical University, Nara, 634-8521, Japan.
6
Department of Medical Informatics and Biomedical Engineering, Shiga University of Medical Science, Shiga, 520-2192, Japan.
7
Department of Pharmacology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
8
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, 113-0033, Japan.
9
Division of Pharmacology, National Institute of Health Sciences, Kawasaki, Kanagawa, 210-9501, Japan.
10
Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan; Department of Bio-informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan. Electronic address: junkokuro@u-shizuoka-ken.ac.jp.

Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a valuable tool to characterize the pharmacology and toxic effects of drugs on heart cells. In particular, hiPSC-CMs can be used to identify drugs that generate arrhythmias. However, it is unclear whether the expression of genes related to generation of CM action potentials differs between hiPSC-CM cell lines and the mature human heart. To address this, we obtained accurate gene expression profiles of commercially available hiPSC-CM cell lines with quantitative real time RT-PCR analysis. Expression analysis of ten cardiac proteins important for generation of action potentials and three cardiac proteins important for muscle contractility was performed using GAPDH for normalization. Comparison revealed large variations in expression levels among hiPSC-CM cell lines and between hiPSC-CMs and normal human heart. In general, gene expression in hiPSC-CM cell lines was more similar to an immature, stem-like cell than a mature cardiomyocyte from human heart samples. These results provide quantitative information about differences in gene expression between hiPSC-CM cell lines, essential for interpreting pharmacology experiments. Our approach can be used as an experimental guideline for future research on gene expression in hiPSC-CMs.

KEYWORDS:

Action potential; Cardiac ion channels; Quantitative real time-PCR; Reference gene; iPS cells

PMID:
31279582
DOI:
10.1016/j.jphs.2019.06.006
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