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Gene Expression Profiling of Functional Murine Embryonic Stem Cell-Derived Cardiomyocytes and Comparison with Adult Heart: Profiling of Murine ESC-Derived Cardiomyocytes

Development Research Center, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Osaka, Japan, Shinozawa_Tadahiro{at}takeda.co.jp

Akiko Tsuji

Development Research Center, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Osaka, Japan

Kenichi Imahashi

Pharmacology Research Laboratories I, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Osaka, Japan

Kosuke Nakashima

Discovery Research Center, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Osaka, Japan

Hiroshi Sawada

Development Research Center, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Osaka, Japan

Hiroyoshi Toyoshiba

Development Research Center, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Osaka, Japan

Satoshi Yamamoto

Animal & Experiment Management Group, Strategic Research & Planning Department, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Osaka, Japan

Kenji Takami

Development Research Center, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Osaka, Japan

Ryoetsu Imai

Development Research Center, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Osaka, Japan

Although embryonic stem cell (ESC)—derived cardiomyocytes may be a powerful tool in drug discovery, their potential has not yet been fully explored. Nor has a detailed comparison with adult heart tissue been performed. We have developed a method for efficient production of cardiomyocyte-rich embryoid bodies (EBs) from murine ESCs. Analysis of global gene expression profiles showed that EBs on day 7 and/or 21 of differentiation (d7CMs and d21CMs, respectively) were similar to adult heart tissue for genes categorized as regulators of muscle contraction or voltage-gated ion channel activity, although d21CMs were more mature than d7CMs for contractile components related to morphological structures. Calcium and sodium channel blockers altered Ca²⁺ transients, and isoproterenol, a β-adrenergic compound, increased the rate of beating in d7CMs and d21CMs. Our gene analytic system therefore enabled us to identify genes that are expressed in the physiological pathways associated with ion channels and structural components in d7CMs and d21CMs. We conclude that EBs might be of use for the basic screening of drugs that might affect contractile function through ion channels. (Journal of Biomolecular Screening 2009:239-245)

Key Words: embryonic stem cells • microarray • adult heart • contraction • ion channels

This version was published on March 1, 2009

Journal of Biomolecular Screening, Vol. 14, No. 3, 239-245 (2009)
DOI: 10.1177/1087057108330112


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