Cardiomyocytes develop from anterior primitive streak cells induced by β-catenin activation and the blockage of BMP signaling in hESCs.
Cardiomyocytes develop from anterior primitive streak cells induced by β-catenin activation and the blockage of BMP signaling in hESCs.
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心肌细胞由 hESC 中 β-连环蛋白激活和 BMP 信号传导阻断诱导的前原条细胞发育而来。
DOI：
10.1111/j.1365-2443.2010.01455.x
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发表时间：
2010
期刊：
影响因子：
2.1
通讯作者：
H
中科院分区：
文献类型：
--
作者：
Yamauchi;K.;Sumi;T.;Minami;I.;Otsuji;T.G.;Kawase;E.;Nakatsuji;N.;Suemori;H
心肌细胞起源于胚胎发生过程中迁移到原始条纹（PS）中前区的细胞。我们之前的研究表明，典型的Wnt/β‐catenin通路信号传导导致人类胚胎干细胞（hESCs）新生PS群体的发育，并且Noggin对Wnt/β‐catenin通路的协同激活和对骨形态发生蛋白（BMP）信号传导的抑制诱导了前PS细胞的形成。本研究表明，在BMP4和成纤维细胞生长因子2 （FGF2）的悬浮培养下，Noggin激活β - catenin诱导的前路PS细胞分化为功能心肌细胞。所有由前PS细胞产生的聚集体都发育成收缩细胞，显示出它们的心脏潜能。每个聚集体中超过30%的细胞是α -肌动蛋白阳性心肌细胞。此外，这些心肌细胞可以很容易地通过简单的大小分离纯化高达80%。相比之下，β - catenin激活诱导的后侧PS细胞没有Noggin，表现出较差的心电位。这些结果表明，心脏谱系蛋白在体外通过与体内心脏发育相似的细胞和分子信号通路发生，从而为研究hESCs早期心脏发育事件提供了有价值的培养模型。
Cardiomyocytes arise from cells that migrate to the mid‐to‐anterior region of the primitive streak (PS) during embryogenesis. We previously showed that canonical Wnt/β‐catenin pathway signaling leads to the development of nascent PS populations from human embryonic stem cells (hESCs) and that synergistic activation of the Wnt/β‐catenin pathway and inhibition of bone morphogenetic protein (BMP) signaling by Noggin induced the formation of anterior PS cells. We herein demonstrate that anterior PS cells induced by the activation of β‐catenin with Noggin differentiate into functional cardiomyocytes when cultured in suspension with BMP4 and fibroblast growth factor 2 (FGF2). All aggregates generated from the anterior PS cells developed into contracting cells demonstrating their cardiac potential. More than 30% of the cells in each aggregate were α‐actinin‐positive cardiomyocytes. In addition, these cardiomyocytes could be easily purified up to 80% by simple size fractionation. In contrast, the posterior PS cells induced by β‐catenin activation without Noggin showed poor cardiac potential. These results show that the commitment to a cardiac lineagein vitrooccurs through similar cellular and molecular signaling pathways involved in cardiac developmentin vivo, thus providing a valuable culture model for studying early cardiac developmental events in hESCs.