The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells
The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells
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DOI：
10.1073/pnas.1323697111
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发表时间：
2014-01-28
影响因子：
11.1
通讯作者：
Willert, Karl
中科院分区：
文献类型：
--
作者：
Fernandez, Antonio;Huggins, Ian J.;Willert, Karl
WNT信号参与维持干细胞处于未分化状态;然而，通常不清楚哪些WNT和WNT受体介导这些活动。在这里，我们研究了WNT受体FZD 7在维持人胚胎干细胞（hESC）在未分化和多能状态中的作用。相对于分化的细胞群体，FZD 7表达在未分化的细胞中显著升高，并且通过短发夹RNA介导的敲低或用针对FZD 7的片段抗原结合（Fab）分子干扰其表达或功能，破坏hESC的多能状态。FZD 7特异性Fab通过下调FZD 7蛋白水平阻断Wnt 3a蛋白的信号传导，表明FZD 7转导Wnt信号以激活Wnt/β-连环蛋白信号传导。这些结果表明，FZD 7编码多能状态的调节因子，并且hESC需要通过FZD 7的内源性WNT/β-连环蛋白信号传导来维持未分化的表型。
WNT signaling is involved in maintaining stem cells in an undifferentiated state; however, it is often unclear which WNTs and WNT receptors are mediating these activities. Here we examined the role of the WNT receptor FZD7 in maintaining human embryonic stem cells (hESCs) in an undifferentiated and pluripotent state. FZD7 expression is significantly elevated in undifferentiated cells relative to differentiated cell populations, and interfering with its expression or function, either by short hairpin RNA-mediated knockdown or with a fragment antigen binding (Fab) molecule directed against FZD7, disrupts the pluripotent state of hESCs. The FZD7-specific Fab blocks signaling by Wnt3a protein by downregulating FZD7 protein levels, suggesting that FZD7 transduces Wnt signals to activate Wnt/beta-catenin signaling. These results demonstrate that FZD7 encodes a regulator of the pluripotent state and that hESCs require endogenous WNT/beta-catenin signaling through FZD7 to maintain an undifferentiated phenotype.