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

Gene Expression Profiling of Functional Murine Embryonic Stem Cell-Derived Cardiomyocytes and Comparison with Adult Heart: Profiling of Murine ESC-Derived Cardiomyocytes
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功能性小鼠胚胎干细胞衍生的心肌细胞的基因表达谱及其与成人心脏的比较:小鼠 ESC 衍生的心肌细胞的谱分析

DOI:
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发表时间:
2009
影响因子:
--
通讯作者:
R. Imai
R. Imai
中科院分区:
化学3区
文献类型:
--
作者:
T. Shinozawa;Akiko Tsuji;K. Imahashi;Kosuke Nakashima;H. Sawada;Hiroyoshi Toyoshiba;Satoshi Yamamoto;K. Takami;R. Imai

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虽然胚胎干细胞(ESC)来源的心肌细胞可能是一个强大的工具,在药物发现,他们的潜力尚未得到充分的探索。也没有与成人心脏组织进行详细的比较。我们开发了一种从小鼠胚胎干细胞中高效生产富含心肌细胞的胚状体(EBs)的方法。全球基因表达谱的分析表明,EB在分化的第7天和/或第21天(分别为d 7 CM和d21 CM)与成人心脏组织的肌肉收缩或电压门控离子通道活性的调节基因相似,尽管d21 CM在与形态结构相关的收缩成分方面比d 7 CM更成熟。钙和钠通道阻滞剂改变了Ca 2+瞬变,异丙肾上腺素(一种β-肾上腺素能化合物)增加了d 7 CM和d21 CM的搏动速率。因此,我们的基因分析系统使我们能够识别在与d 7 CM和d21 CM中的离子通道和结构组分相关的生理途径中表达的基因。我们的结论是,EB可能是用于基本筛选药物,可能会影响收缩功能,通过离子通道。(Journal of Biomolecular Screening 2009:239-245)
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)
DOI: 10.1073/pnas.95.6.2979
发表时间: 1998-03-17
影响因子: 11.1
作者:
Claycomb, WC;Lanson, NA;Izzo, NJ
通讯作者: Izzo, NJ