Postnatal isl1+cardioblasts enter fully differentiated cardiomyocyte lineages
Postnatal isl1+cardioblasts enter fully differentiated cardiomyocyte lineages
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DOI：
10.1038/nature03215
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发表时间：
2005-02-10
期刊：
影响因子：
64.8
通讯作者：
Chien, KR
中科院分区：
文献类型：
--
作者：
Laugwitz, KL;Moretti, A;Chien, KR
天然心脏祖细胞的纯化、更新和分化将为解开心肌细胞谱系形成的步骤及其与各种先天性和成人心脏病的联系提供机制支持(1-3)。到目前为止，几乎没有证据表明出生后的心脏中存在天然的心脏前体细胞(4)。在此，我们报道了在出生后的大鼠、小鼠和人的心肌中鉴定Isl1(+)心脏祖细胞。心脏间充质滋养层允许更新分离的祖细胞，同时保持其采用完全分化的心肌细胞表型的能力。他莫昔芬诱导的CRE/LOX技术能够在规定的时间选择性地标记包括其后代在内的祖细胞群体，并将其纯化到相对同质性。与新生心肌细胞共培养的研究表明，Isl1(+)细胞代表真正的内源性心脏前体细胞(成心细胞)，在没有细胞融合、完整的钙循环和动作电位产生的情况下，可以高效地转化为成熟的心脏表型，并稳定表达肌细胞标志物(25%)。天然成心细胞的发现代表了一种基于遗传的系统，用于识别发育和疾病中心脏细胞谱系形成和成熟的步骤。
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.