胚胎期肝脏发育是一个被精细调控的过程，基因在这个过程中被有规律的开放和关闭，有证据表明许多胎肝期特异性高表达的分子在肝癌组织中上调表达，胚胎期肝脏和肝癌具有共同调控通路，基于以上分析，本课题前期用芯片技术连续观察了肝脏各发育阶段中lncRNA和mRNA表达，发现大量胎肝特异性高表达lncRNA，其中H19、Pvt1等在肝癌组织中的异常表达被确认，其参与调控的表观遗传学机制也部分被揭示，在此基础上，本课题拟利用肝干细胞、胚胎干细胞及其诱导生成的中胚层和肝样细胞，从候选lncRNA中筛选出与肝发育-肝干细胞分化-肝癌干细胞生成相关的核心lncRNA，利用基因克隆、RNA干扰、ChIP、RIP等技术在体外培养的肝细胞、肝干细胞、诱导的肝样细胞及lncRNA基因敲除细胞、小鼠中深入研究核心lncRNA参与的表观遗传学调控机制，为肝癌诊断找到更敏感检测指标，为肝癌治疗确定新靶点。以上内容经检索无报道

Embryonic liver development is a fine-tuning process. Genes in this process are the opening and closing orderly, there are evidences indicating that some genes with high expression in fetal liver are also highly expressed in hepatocellular carcinoma and some signaling pathways exist both in fetal liver and hepatocellular carcinoma. In the early stage of this project we have found a large number of lncRNAs with high expression specificly in fetal liver, some of which have been comfirmed upregulated or downregulated in hepatocellular cacinoma, such as Pvt1 and H19. The roles of some lncRNAs in the epigenetic regulation mechanism are also unveiled. On the basis above, we intend to pick out the lncRNAs which relate to liver development, hepatoblast differentiation and hepatocarcinoma stem cell from our chip results by using the materials of cultured hepatic stem cells, embryonic stem cells, induced mesodermal cells and hepatocyte-like cells induced from embryonic stem cells in vitro. Then in order to find some more sensitive markers of liver cancer and targets against liver cancer, we plan to investigate their function in epigenetic regulation by utilizing the methods of gene clone, RNA interference, ChIP and RIP in hepatocytes, hepatic stem cells, induced hepatocyte-like cells, lncRNA gene knockout cells and lncRNA gene knockout mice.By now, no similar research was reproted through bibliographic retrieval.