转录因子GATA4和Foxa2在调控内胚层细胞肝向分化中的相互作用

项目名称： 转录因子GATA4和Foxa2在调控内胚层细胞肝向分化中的相互作用

项目编号： No.31271469

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 王欣

作者单位： 内蒙古大学

项目金额： 90万元

中文摘要： 转录因子GATA4和Foxa2在肝脏器官发生中决定了内胚层细胞向肝细胞分化的命运。然而，由于不能从胚胎组织中分离到足够数量、发育同步的内胚层细胞和肝前体细胞，长期以来无法实施对GATA4和Foxa2下游靶基因的研究，也无法在全基因组水平证明GATA4和Foxa2的先锋因子作用。胚胎干细胞的肝向诱导分化可以重演胚胎肝脏器官发生过程，可获得足够的内胚层细胞和肝前体细胞。本课题应用ChIP-Seq技术，在全基因组水平研究Foxa2和GATA4靶基因，以期获得肝向分化中的未知基因，并在全基因组水平上证明Foxa2和GATA4作为先锋因子的表观调控作用。另外，本申请还将研究Tcf12与GATA4和Foxa2互相结合以及结合位点间的相互关系。对GATA4和Foxa2相互作用的认识，有助于阐明其作为关键转录因子在肝向分化中转录调控方面的分子机理，有助于指导干细胞肝向分化向正确和高效的细胞产业化方向发展。

中文关键词： 肝脏发生；转录调控；Foxa2；Gata4；ChIP-Seq

英文摘要： Transcription factors play the important roles in guiding the hepatic fate of embryonic endoderm cells by controlling the relative gene transcription events. Study on the activities of some key transcription factors during hepatic differentiation will be helpful for elucidation of mechanism of liver organogenesis. Previously, it has been known that GATA4 and Foxa2, as key transcription factors, could determine the hepatic fate of embryonic endoderm cells during liver organogenesis or hepatogenesis. However, the target genes of two transcription factors during the critical process of hepatogenesis could not be known because there were no sufficient and synchronized embryonic endoderm cells that could be used in molecular study. For the same reason, the proposed hypothesis of GATA4 and Foxa2 as "pioneer factors" during hepatogenesis has not been proved genome-widely. Recently, we have found that the in vitro hepatic differentiation of ES cells could mimic the process of embryonic hepatogenesis. During the hepatic induction process of ES cells, we can generate sufficient ES cell-derived definitive endoderm cells and ES cell-derived hepatic progenitor cells. With enough cells in ChIP-seq analysis, we can use the high though-put DNA sequencing to collectively discover the target genes of both GATA4 and Foxa2. This st

英文关键词： Liver organogenesis；Transcription factor；Foxa2；Gata4；ChIP-Seq