Identification of Pathways Regulating Hepatocyte Differentiation from iPS Cells

 描述(由申请人提供)：我们之前已经证明，我们可以从人类多能干细胞中培养出具有许多肝细胞特征的细胞。这一过程与哺乳动物肝脏发育过程密切相关。细胞的分化是同步的，可重复的，高效的，可以为发现调节人类肝细胞形成的新途径提供基础。因此，我们建议利用这种细胞分化系统作为一个平台来筛选可能影响肝脏祖细胞形成的小分子。我们相信，该提案的成功将揭示有助于在培养中从人类多能干细胞形成肝细胞的细胞过程和分子途径。这样的发现将有助于理性的 为肝脏疾病的研究和治疗提供临床相关的肝细胞，并为肝脏的发育提供新的机制见解的方案的设计。

 DESCRIPTION (provided by applicant): 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.