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

Masami Kodama1, Kazuharu Furutani2, Reiko Kimura3

  • 1Department 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.

Journal of Pharmacological Sciences
|July 8, 2019
PubMed

Insights

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) show significant gene expression variations compared to mature heart cells. This study quantifies these differences, crucial for interpreting drug effects in hiPSC-CM research.

Area of Science:

  • Cardiology
  • Stem Cell Biology
  • Pharmacology

Background:

  • Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are vital for drug testing and toxicity studies, particularly for identifying arrhythmia-inducing agents.
  • Understanding the gene expression profiles of hiPSC-CMs is critical for accurate interpretation of their use in preclinical drug development.
  • Existing knowledge gaps concern the comparability of hiPSC-CM gene expression related to cardiac action potentials versus the mature human heart.

Purpose of the Study:

  • To quantitatively assess and compare gene expression profiles of commercially available hiPSC-CM cell lines.
  • To determine if hiPSC-CMs accurately reflect the gene expression of mature human cardiomyocytes regarding action potential and contractility proteins.
  • To provide a guideline for future research on hiPSC-CM gene expression.

Main Methods:

  • Quantitative real-time RT-PCR analysis was employed to obtain accurate gene expression profiles.
  • Expression levels of ten cardiac proteins involved in action potential generation and three for muscle contractility were analyzed.
  • GAPDH was used as the normalization reference gene for all expression analyses.

Main Results:

  • Significant variations in gene expression were observed among different hiPSC-CM cell lines.
  • hiPSC-CMs exhibited substantial differences in gene expression compared to normal human heart samples.
  • Gene expression in hiPSC-CMs generally resembled immature, stem-like cells rather than mature cardiomyocytes.

Conclusions:

  • hiPSC-CMs display considerable heterogeneity in gene expression, impacting their utility as a model for mature human heart cells.
  • The observed gene expression patterns suggest hiPSC-CMs may not fully recapitulate the mature cardiomyocyte phenotype.
  • These findings are essential for the accurate interpretation of pharmacological and toxicological data derived from hiPSC-CM studies.
Keywords:
Action potentialCardiac ion channelsQuantitative real time-PCRReference geneiPS cells

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