Sca-1 knockout impairs myocardial and cardiac progenitor cell function.
Sca-1 knockout impairs myocardial and cardiac progenitor cell function.
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DOI：
10.1161/circresaha.112.274662
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发表时间：
2012-08-31
影响因子：
20.1
通讯作者：
Sussman MA
中科院分区：
文献类型：
--
作者：
Bailey B;Fransioli J;Gude NA;Alvarez R Jr;Zhang X;Gustafsson ÅB;Sussman MA
心脏祖细胞对于维持心肌结构和功能是重要的，但是控制这些祖细胞的分子机制仍然不清楚，需要阐明以增强再生治疗方法。使用Sca-1敲除/绿色荧光蛋白敲入报告基因小鼠（ScaKI），了解干细胞抗原-1（Sca-1）缺失对c-kit+心脏祖细胞功能特性和心肌性能的影响。Sca-1基因缺失导致早发性心脏收缩功能缺陷，如超声心动图和血流动力学以及年龄相关性肥大所确定的。ScaKI小鼠中的常驻心脏祖细胞对体内病理损伤没有反应，这与ScaKI心脏祖细胞体外生长和存活受损的观察结果一致。ScaKI心脏祖细胞缺陷的分子基础与经典Wnt信号通路激活的增加有关，这与谱系定型的分子特征一致。Sca-1基因缺失导致心肌收缩力和修复的原发性心脏缺陷，这与与改变的经典Wnt信号相关的常驻心脏祖细胞增殖能力受损一致。
Cardiac progenitor cells are important for maintenance of myocardial structure and function, but molecular mechanisms governing these progenitor cells remain obscure and require elucidation to enhance regenerative therapeutic approaches. To understand consequences of stem cell antigen-1 (Sca-1) deletion upon functional properties of c-kit+ cardiac progenitor cells and myocardial performance using a Sca-1 knockout/Green Fluorescent Protein knock-in reporter mouse (ScaKI). Genetic deletion of Sca-1 results in early-onset cardiac contractile deficiency as determined by echocardiography and hemodynamics as well as age-associated hypertrophy. Resident cardiac progenitor cells in ScaKI mice do not respond to pathological damage in vivo, consistent with observations of impaired growth and survival of ScaKI cardiac progenitor cells in vitro. The molecular basis of the defect in ScaKI cardiac progenitor cells is associated with increased canonical Wnt signaling pathway activation consistent with molecular characteristics of lineage commitment. Genetic deletion of Sca-1 causes primary cardiac defects in myocardial contractility and repair consistent with impairment of resident cardiac progenitor cell proliferative capacity associated with altered canonical Wnt signaling.