Identification of Pathways Regulating Hepatocyte Differentiation from iPS Cells

项目总结： 我们之前已经证明，我们可以生产出具有许多共同特征的细胞 来自人类多能干细胞的肝细胞。这一过程与所发生的情况密切相关 在哺乳动物的肝脏发育过程中。细胞的分化是同步的， 可重复性和高效率，并可为发现新的途径提供基础， 调节人肝细胞的形成。因此，我们建议使用这种蜂窝 分化系统作为筛选可能影响形成的小分子的平台 肝脏祖细胞的数量。我们相信，该提案的成功将揭示细胞过程 以及有助于人类多能性形成肝细胞的分子途径 培养中的干细胞。这些发现将有助于合理设计能够产生 为肝病的研究和治疗提供临床相关的肝细胞 对肝脏发育的新机制洞察。

Project Summary: We have shown previously that we can produce cells that share many of the characteristics of hepatocytes from human pluripotent stem cells. The process closely mirrors that which occurs during liver development in mammals. The differentiation of the cells is synchronous, reproducible, and efficient and could provide a basis for the discovery of novel pathways that regulate the formation of human hepatocytes. We therefore propose to use this cellular differentiation system as a platform to screen for small molecules that can impact the formation of hepatic progenitors. We believe that success in the proposal will uncover cellular processes and molecular pathways that contribute to the formation of hepatocytes from human pluripotent stem cells in culture. Such findings will aid in the rational design of protocols that can produce clinically relevant hepatocytes for the study and treatment of hepatic disease as well as provide new mechanistic insight into development of the liver.