Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling
Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling
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DOI：
10.1073/pnas.0806522105
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发表时间：
2008-08-26
影响因子：
11.1
通讯作者：
Iredale, John P.
中科院分区：
文献类型：
--
作者：
Hay, David C.;Fletcher, Judy;Iredale, John P.
人胚胎干细胞（hESCs）是多能原代细胞的重要来源。然而，迄今为止，在体外将其同质细胞分化为特定细胞类型已被证明是困难的。Wnt信号已被证明在协调发育中发挥重要作用，我们证明Wnt3a在体内人类肝脏发育的关键阶段存在差异表达。Wnt3a在hESCs肝细胞分化中的重要作用与我们的体外模型相似，证明了生理途径对细胞分化的重要性。我们的研究提供了令人信服的证据，证明Wnt3a信号对于体外和体内的肝细胞功能协调很重要。此外，我们证明Wnt3a促进了hESCs克隆镀，表现出功能性肝分化。这些研究代表了利用hesc来源的肝细胞进行人类肝功能高通量代谢分析的重要一步。
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.