我们研究发现肝细胞体外定向诱导会发生EMT/MET现象，敲除SNAI1会阻碍成熟肝细胞的产生，可见EMT/MET过程与细胞命运紧密相关。与肝脏类似，肠组织也来源于内胚层，肠上皮定向诱导也会经历类似的EMT/MET过程。OVOL家族蛋白可通过影响相关转录因子的表达抑制MET过程。肝分化研究发现MET阶段OVOL1/2表达量显著高于EMT阶段，因此推测OVOL1/2在肝分化MET过程中扮演重要角色。我们拟采用基因敲除技术构建OVOL1/2敲除干细胞系，将其分别定向诱导为肠组织或肝上皮，揭示其在两种分化模型中的作用。采用化合物或siRNA模拟或修复基因敲除所致的表型缺陷，阐明MET对细胞命运的调控作用。

Our previous study shows that a sequential EMT-MET mechanism drives the differentiation of human embryonic stem cells towards hepatocytes. Genetic ablation of SNAI1 in hESCs completely disrupts the formation of DE and harvest of mature hepatocytes. It is quite obvious that the EMT-MET process relates tightly to cell fates. Similar to the liver, intestinal tissues are also endoderm-derived organs. The in vitro differentiation of intestinal epithelia may also undergo a sequential EMT-MET mechanism, making them the best models for studying EMT/MET regulators. It is reported that proteins of OVOL family play important roles in inhibiting MET process mainly via inhibition of EMT transcription factors’ expression. According to our RNAseq data on hepatocyte differentiation, we find lower expression of OVOL1/2 genes in an EMT process, while higher expression of those in later MET process. Thus we speculate that OVOL1/2 may play important roles in a later MET process. We intend to ablate OVOL1/2 geneticly in hESCs, and induce them into intestinal tissues or hepatocyte in vitro. It will be our main task to discover the discrepency between wild-type hESCs derived intestinal organoid or hepatocytes and OVOL1/2 knock-out hESCs derived ones. We will further screen small chemical molecules or siRNA to imitate defects in phenotype or to rescue phenotye defects by OVOL1/2 deletion. Our study try to elucidate the important role of MET-related factors OVOL1/2 in intestinal organoid and liver differentiation, as well as the role of MET process in cell fates.