Gene expression profiling of functional murine embryonic stem cell-derived cardiomyocytes and comparison with adult heart: profiling of murine ESC-derived cardiomyocytes.
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 beta-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.
Shinozawa
Tadahiro
T
Development Research Center, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Osaka, Japan. Shinozawa_Tadahiro@takeda.co.jp
Tsuji
Akiko
A
Imahashi
Kenichi
K
Nakashima
Kosuke
K
Sawada
Hiroshi
H
Toyoshiba
Hiroyoshi
H
Yamamoto
Satoshi
S
Takami
Kenji
K
Imai
Ryoetsu
R
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D007150:Immunohistochemistry; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D009200:Myocardial Contraction / Q000187:drug effects / Q000235:genetics; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D025341:Principal Component Analysis; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D002121:Calcium Channel Blockers; D007473:Ion Channels; D007545:Isoproterenol; D002118:Calcium