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c-kit~+ cells minimally contribute cardiomyocytes to the heart

机译:c-kit〜+细胞对心肌的贡献最小

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摘要

If and how the heart regenerates after an injury event is highly debated, c-kit-expressing cardiac progenitor cells have been reported as the primary source for generation of new myocardium after injury. Here we generated two genetic approaches in mice to examine whether endogenous c-kit~+ cells contribute differentiated cardiomyocytes to the heart during development, with ageing or after injury in adulthood. A complementary DNA encoding either Cre recombinase or a tamoxifen-inducible MerCreMer chimaeric protein was targeted to the Kit locus in mice and then bred with reporter lines to permanently mark cell lineage. Endogenous c-kit~+ cells did produce new cardiomyocytes within the heart, although at a percentage of approximately 0.03 or less, and if a preponderance towards cellular fusion is considered, the percentage falls to below approximately 0.008. By contrast, c-kit~+ cells amply generated cardiac endothelial cells. Thus, endogenous c-kit~+ cells can generate cardiomyocytes within the heart, although probably at a functionally insignificant level.%表达酪氨酸激酶/原致癌基因c-kit的内源性心脏祖细胞一直被认为是受伤后生成新的心肌的主要来源,但用成年心脏固有的c-kit细胞所做的其他研究却报告了相反的结果: 这些细胞在活体中不能产生心肌细胞。Jeffrey Molkentin及同事利用一个可诱导的世系跟踪系统对这一问题进行了研究。他们发现,心肌细胞从c-kit~+世系形成的速度极慢,在生理学上没有多大意义。相比之下,c-kit~+细胞对心脏中内皮细胞的生成有实质性贡献。
机译:损伤事件后心脏是否再生以及如何再生一直存在争议,据报道表达c-kit的心脏祖细胞是损伤后产生新心肌的主要来源。在这里,我们在小鼠中产生了两种遗传学方法,以检查内源性c-kit〜+细胞是否在发育过程中,衰老或成年后的心脏中向心脏贡献分化的心肌细胞。将编码Cre重组酶或他莫昔芬诱导的MerCreMer嵌合蛋白的互补DNA靶向小鼠的Kit基因座,然后与报告基因系进行育种以永久标记细胞谱系。内源性c-kit +细胞确实在心脏内产生了新的心肌细胞,尽管其百分比约为0.03或更低,并且如果考虑到细胞融合的优势,该百分比将降至约0.008以下。相比之下,c-kit〜+细胞可大量产生心脏内皮细胞。因此,内源性c-kit〜+细胞可以在心脏内产生心肌细胞,尽管在功能上可能是微不足道的。%表达酪氨酸激酶/原致癌基因c-kit的内源性心脏祖细胞一直被认为是受伤后杰弗里·莫肯汀(Jeffrey Molkentin)和同事利用一个可诱导的世系他们发现,心肌细胞从c-kit〜+世系形成的速度极慢,在生理学上没有多大意义。根据之下,c-kit〜+细胞对心脏中膜细胞的生成有实质性贡献。

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  • 来源
    《Nature》 |2014年第7500期|337-341a1|共6页
  • 作者单位

    Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA,Department of Medicine, division of Cardiology, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA;

    Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA;

    Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA;

    Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA;

    Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA;

    Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA;

    Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, California 90048, USA;

    Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, California 90048, USA;

    Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA,Howard Hughes Medical Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, 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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