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首页> 外文期刊>Nature Genetics >Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration
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Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration

机译：单核二倍体心肌细胞的频率下潜心脏再生的自然变化

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摘要

Adult mammalian cardiomyocyte regeneration after injury is thought to be minimal. Mononuclear diploid cardiomyocytes (MNDCMs), a relatively small subpopulation in the adult heart, may account for the observed degree of regeneration, but this has not been tested. We surveyed 120 inbred mouse strains and found that the frequency of adult mononuclear cardiomyocytes was surprisingly variable (>7-fold). Cardiomyocyte proliferation and heart functional recovery after coronary artery ligation both correlated with pre-injury MNDCM content. Using genome-wide association, we identified Tnni3k as one gene that influences variation in this composition and demonstrated that Tnni3k knockout resulted in elevated MNDCM content and increased cardiomyocyte proliferation after injury. Reciprocally, overexpression of Tnni3k in zebrafish promoted cardiomyocyte polyploidization and compromised heart regeneration. Our results corroborate the relevance of MNDCMs in heart regeneration. Moreover, they imply that intrinsic heart regeneration is not limited nor uniform in all individuals, but rather is a variable trait influenced by multiple genes.
机译：伤害后的成人哺乳动物心肌细胞再生被认为是最小的。单核二倍体心肌细胞（MNDCMS），成年人心脏的相对小的亚群，可能会占观察到的再生程度，但这尚未测试。我们调查了120次近交小鼠菌株，发现成人单核心肌细胞的频率令人惊讶的变量（> 7倍）。冠状动脉结扎后心肌细胞增殖和心功能恢复与损伤前损伤MNDCM含量相关。使用基因组关联，我们将TNNI3K鉴定为一种影响该组合物变异的一个基因，并证明TNNI3K敲除导致损伤后的MNDCM含量升高并增加心肌细胞增殖增加。相互作用，在斑马鱼中的TNNI3K过表达促进心肌细胞多倍化和损伤心脏再生。我们的结果证实了MNDCMS在心脏再生中的相关性。此外，它们意味着在所有个体中，内在心脏再生不受限制，而是是受多种基因影响的可变性状。

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  • 来源
    《Nature Genetics》 |2017年第9期|共11页
  • 作者

    Patterson Michaela; Barske Lindsey; Van Handel Ben; Rau Christoph D.; Gan Peiheng; Sharma Avneesh; Parikh Shan; Denholtz Matt; Huang Ying; Yamaguchi Yukiko; Shen Hua; Allayee Hooman; Crump J. Gage; Force Thomas I.; Lien Ching-Ling; Makita Takako; Lusis Aldons J.; Kumar S. Ram; Sucov Henry M.;

  • 作者单位

    Univ Southern Calif Keck Sch Med Dept Stem Cell Biol &

    Regenerat Med Los Angeles CA 90033 USA;

    Univ Southern Calif Keck Sch Med Dept Stem Cell Biol &

    Regenerat Med Los Angeles CA 90033 USA;

    Univ Southern Calif Keck Sch Med Dept Stem Cell Biol &

    Regenerat Med Los Angeles CA 90033 USA;

    Univ Calif Los Angeles David Geffen Sch Med Dept Human Genet Los Angeles CA 90095 USA;

    Univ Southern Calif Keck Sch Med Dept Stem Cell Biol &

    Regenerat Med Los Angeles CA 90033 USA;

    Univ Southern Calif Keck Sch Med Dept Stem Cell Biol &

    Regenerat Med Los Angeles CA 90033 USA;

    Vanderbilt Univ Med Ctr Div Cardiovasc Med Nashville TN USA;

    Univ Calif Los Angeles David Geffen Sch Med Dept Biol Chem Los Angeles CA 90095 USA;

    Childrens Hosp Los Angeles Saban Res Inst Program Dev Biol &

    Regenerat Med Los Angeles CA 90027;

    Univ Southern Calif Keck Sch Med Dept Stem Cell Biol &

    Regenerat Med Los Angeles CA 90033 USA;

    Univ Southern Calif Keck Sch Med Dept Stem Cell Biol &

    Regenerat Med Los Angeles CA 90033 USA;

    Univ Southern Calif Keck Sch Med Dept Prevent Med Los Angeles CA 90033 USA;

    Univ Southern Calif Keck Sch Med Dept Stem Cell Biol &

    Regenerat Med Los Angeles CA 90033 USA;

    Vanderbilt Univ Med Ctr Div Cardiovasc Med Nashville TN USA;

    Childrens Hosp Los Angeles Saban Res Inst Program Dev Biol &

    Regenerat Med Los Angeles CA 90027;

    Childrens Hosp Los Angeles Dev Neurosci Program Saban Res Inst Los Angeles CA 90027 USA;

    Univ Calif Los Angeles David Geffen Sch Med Dept Human Genet Los Angeles CA 90095 USA;

    Univ Southern Calif Keck Sch Med Dept Surg Los Angeles CA 90033 USA;

    Univ Southern Calif Keck Sch Med Dept Stem Cell Biol &

    Regenerat Med Los Angeles CA 90033 USA;

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  • 正文语种 eng
  • 中图分类 医学遗传学;
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