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

Masami Kodama, Kazuharu Furutani, R. Kimura, Tomoko Ando, Kazuho Sakamoto, Shushi Nagamori, Takashi Ashihara, Yoshihisa Kurachi, Yuko Sekino, Tetsushi Furukawa, Yasunari Kanda, J. Kurokawa

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
JournalJournal of Pharmacological Sciences
DOIs
StatePublished - Jan 1 2019

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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    Kodama, M., Furutani, K., Kimura, R., Ando, T., Sakamoto, K., Nagamori, S., Ashihara, T., Kurachi, Y., Sekino, Y., Furukawa, T., Kanda, Y., & Kurokawa, J. (2019). Systematic expression analysis of genes related to generation of action potentials in human iPS cell-derived cardiomyocytes. Journal of Pharmacological Sciences. https://doi.org/10.1016/j.jphs.2019.06.006