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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors
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Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors

机译：典型的Wnt信号是哺乳动物心脏祖细胞的正向调节剂。

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Guiding multipotent cells into distinct lineages and controlling their expansion remain fundamental challenges in developmental and stem cell biology. Members of the Wnt pathway control many pivotal embryonic events, often promoting self-renewal or expansion of progenitor cells. In contrast, canonical Wnt ligands are thought to negatively regulate cardiomyogenesis in several species. However, the cell-autonomous role of canonical Wnt signaling within precardiac mesoderm, through its obligatory transcriptional mediator, β-catenin, is unknown. Using tissue-specific in vivo genetic manipulation, we found that β-catenin is required for development of cardiac progenitors and is a positive regulator of proliferative expansion of such progenitor cells. At discrete windows of development in embryonic stem cells, activation of canonical Wnt signaling promoted expansion of cardiac progenitors after initial commitment and was required for cardiac differentiation. Together, these data provide in vivo and in vitro evidence that canonical Wnt signaling promotes the expansion of cardiac progenitors and differentiation of cardiomyocytes.
机译：将多能细胞分为不同的谱系并控制其扩增仍然是发育和干细胞生物学的基本挑战。 Wnt通路的成员控制着许多关键的胚胎事件，通常促进祖细胞的自我更新或扩增。相比之下，经典的Wnt配体被认为对几种物种的心肌发生负调控。但是，尚不清楚通过其强制性转录介体β-catenin在心脏前中胚层中经典Wnt信号传导的细胞自主作用。使用组织特异性的体内遗传操作，我们发现β-catenin是心脏祖细胞发育所必需的，并且是此类祖细胞增殖扩展的积极调节剂。在胚胎干细胞发育的不连续窗口中，经典的Wnt信号激活在最初承诺后促进了心脏祖细胞的扩增，这是心脏分化所必需的。总之，这些数据提供了体内和体外的证据，表明经典的Wnt信号传导可促进心脏祖细胞的扩增和心肌细胞的分化。

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