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Postnatal isl1+cardioblasts enter fully differentiated cardiomyocyte lineages

机译:产后isl1 +成纤维细胞进入完全分化的心肌细胞谱系

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The purification, renewal and differentiation of native cardiac progenitors would form a mechanistic underpinning for unravelling steps for cardiac cell lineage formation, and their links to forms of congenital and adult cardiac diseases(1 - 3). Until now there has been little evidence for native cardiac precursor cells in the postnatal heart(4). Herein, we report the identification of isl1(+) cardiac progenitors in postnatal rat, mouse and human myocardium. A cardiac mesenchymal feeder layer allows renewal of the isolated progenitor cells with maintenance of their capability to adopt a fully differentiated cardiomyocyte phenotype. Tamoxifen- inducible Cre/ lox technology enables selective marking of this progenitor cell population including its progeny, at a defined time, and purification to relative homogeneity. Coculture studies with neonatal myocytes indicate that isl1(+) cells represent authentic, endogenous cardiac progenitors ( cardioblasts) that display highly efficient conversion to a mature cardiac phenotype with stable expression of myocytic markers ( 25%) in the absence of cell fusion, intact Ca2+- cycling, and the generation of action potentials. The discovery of native cardioblasts represents a genetically based system to identify steps in cardiac cell lineage formation and maturation in development and disease.
机译:天然心脏祖细胞的纯化,更新和分化将为揭示心脏细胞谱系形成的步骤及其与先天性和成年心脏疾病形式的联系提供机械基础(1-3)。迄今为止,几乎没有证据表明产后心脏中存在天然的心脏前体细胞(4)。在这里,我们报告了在产后大鼠,小鼠和人类心肌中的isl1(+)心脏祖细胞的鉴定。心脏间质饲养层允许更新分离的祖细胞,并保持其采用完全分化的心肌表型的能力。他莫昔芬诱导的Cre / lox技术可在限定的时间选择性标记该祖细胞群(包括其后代),并纯化至相对均一。与新生儿心肌细胞的共培养研究表明,isl1(+)细胞代表真实的内源性心脏祖细胞(成心脏细胞),在没有细胞融合且完整的Ca2 +的情况下,可以高效转化为具有稳定的心肌细胞标记物(25%)的成熟心脏表型。 -循环运动,并产生动作电位。天然成心脏细胞的发现代表了一种基于遗传的系统,可识别心脏细胞谱系形成和发育及疾病成熟的步骤。

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