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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling
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Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling

机译：hESCs向功能性肝内胚层的高效分化需要ActivinA和Wnt3a信号传导

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摘要

Human embryonic stem cells (hESCs) are a valuable source of pluripotential primary cells. To date, however, their homogeneous cellular differentiation to specific cell types in vitro has proven difficult. Wnt signaling has been shown to play important roles in coordinating development, and we demonstrate that Wnt3a is differentially expressed at critical stages of human liver development in vivo. The essential role of Wnt3a in hepatocyte differentiation from hESCs is paralleled by our in vitro model, demonstrating the importance of a physiologic approach to cellular differentiation. Our studies provide compelling evidence that Wnt3a signaling is important for coordinated hepatocellular function in vitro and in vivo. In addition, we demonstrate that Wnt3a facilitates clonal plating of hESCs exhibiting functional hepatic differentiation. These studies represent an important step toward the use of hESC-derived hepatocytes in high-throughput metabolic analysis of human liver function.
机译：人胚胎干细胞（hESCs）是多潜能原代细胞的重要来源。然而，迄今为止，已证明它们难以在体外将细胞均匀分化为特定细胞类型。已经显示出Wnt信号传导在协调发育中起重要作用，并且我们证明了Wnt3a在体内人肝发育的关键阶段差异表达。 Wnt3a在hESCs分化为肝细胞中的重要作用与我们的体外模型相似，表明了生理学方法对细胞分化的重要性。我们的研究提供了令人信服的证据，表明Wnt3a信号对于在体内和体外协调肝细胞功能很重要。此外，我们证明Wnt3a促进功能肝分化的hESCs的克隆电镀。这些研究代表了在人类肝脏功能的高通量代谢分析中使用hESC来源的肝细胞的重要一步。

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