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Mammalian heart renewal by pre-existing cardiomyocytes

机译：通过已有的心肌细胞进行哺乳动物心脏更新

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摘要

在心血管领域，关于在整个成年期哺乳动物心脏平衡过程中现有心肌细胞的更替相对于祖细胞贡献的程度存在争议。这项研究采用一个新方法来解决这种争议：将“前瞻性标记”与氮-15同位素和基因脉冲跟踪相结合来测定成年哺乳动物心脏中的DNA合成。本文作者的结论是，在正常衰老过程中，事先存在的心肌细胞是正常哺乳动物心肌平衡中心肌细胞更替的支配性来源--在从心肌梗塞恢复过程中，心肌细胞更替增加五倍。%Although recent studies have revealed that heart cells are generated in adult mammals, the frequency of generation and the source of new heart cells are not yet known. Some studies suggest a high rate of stem cell activity with differentiation of progenitors to cardiomyocytes. Other studies suggest that new cardiomyocytes are born at a very low rate, and that they may be derived from the division of pre-existing cardiomyocytes. Here we show, by combining two different pulse-chase approaches-genetic fate-mapping with stable isotope labelling, and multi-isotope imaging mass spectrometry-that the genesis of cardiomyocytes occurs at a low rate by the division of pre-existing cardiomyocytes during normal ageing, a process that increases adjacent to areas of myocardial injury. We found that cell cycle activity during normal ageing and after injury led to polyploidy and multinudeation, but also to new diploid, mononucleate cardiomyocytes. These data reveal pre-existing cardiomyocytes as the dominant source of cardiomyocyte replacement in normal mammalian myocardial homeostasis as well as after myocardial injury.
机译：在心血管领域，关于在整个成年期哺乳动物心脏平衡过程中现有心肌细胞的更替相对于祖细胞贡献的程度存在争议。这项研究采用一个新方法来解决这种争议：将“前瞻性标记”与氮-15同位素和基因脉冲跟踪相结合来测定成年哺乳动物心脏中的DNA合成。本文作者的结论是，在正常衰老过程中，事先存在的心肌细胞是正常哺乳动物心肌平衡中心肌细胞更替的支配性来源--在从心肌梗塞恢复过程中，心肌细胞更替增加五倍。%Although recent studies have revealed that heart cells are generated in adult mammals, the frequency of generation and the source of new heart cells are not yet known. Some studies suggest a high rate of stem cell activity with differentiation of progenitors to cardiomyocytes. Other studies suggest that new cardiomyocytes are born at a very low rate, and that they may be derived from the division of pre-existing cardiomyocytes. Here we show, by combining two different pulse-chase approaches-genetic fate-mapping with stable isotope labelling, and multi-isotope imaging mass spectrometry-that the genesis of cardiomyocytes occurs at a low rate by the division of pre-existing cardiomyocytes during normal ageing, a process that increases adjacent to areas of myocardial injury. We found that cell cycle activity during normal ageing and after injury led to polyploidy and multinudeation, but also to new diploid, mononucleate cardiomyocytes. These data reveal pre-existing cardiomyocytes as the dominant source of cardiomyocyte replacement in normal mammalian myocardial homeostasis as well as after myocardial injury.

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  • 来源
    《Nature》 |2013年第7432期|433-436qt5|共5页
  • 作者

    Samuel E. Senyo; Matthew L. Steinhauser; Christie L. Pizzimenti; Vicky K. Yang; Lei Cai; Mei Wang; Ting-Di Wu; Jean-Luc Guerquin-Kern; Claude P. Lechene; Richard T. Lee;

  • 作者单位

    Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts 02139, USA;

    Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts 02139, USA;

    Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts 02139, USA;

    Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts 02139, USA;

    Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts 02139, USA;

    National Resource for Imaging Mass Spectrometry, Cambridge, Massachusetts 02139, USA,Harvard Stem Cell Institute, Cambridge, Massachusetts 02139, USA;

    INSERM U.759,91405 Orsay, France,lnstitut Curie, Laboratoire de Microscopie lonique, 91405 Orsay, France;

    INSERM U.759,91405 Orsay, France,lnstitut Curie, Laboratoire de Microscopie lonique, 91405 Orsay, France;

    National Resource for Imaging Mass Spectrometry, Cambridge, Massachusetts 02139, USA,Genetics Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts 02139, USA;

    Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts 02139, USA,Harvard Stem Cell Institute, Cambridge, Massachusetts 02139, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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