肝静脉闭塞病是造血干细胞移植的严重并发症，其发生风险及严重程度受肝细胞修复程度的影响。Notch1信号是肝细胞修复的重要信号通路之一。既往研究侧重于Notch1通路的下游调控，而其自身表达调控尚待探索。长链非编码RNA（lncRNA）是基因表达调控的新着眼点，我们发现lncRNA 0610009E02Rik与Notch1同源；造血干细胞移植小鼠肝损伤模型中肝细胞内0610009E02Rik与Notch1同步下降，二者呈正相关。提示该lncRNA是Notch1的正性调节子，可调控Notch1表达影响肝损伤的修复。本课题拟采用肝细胞损伤离体和在体模型，明确0610009E02Rik在损伤肝细胞修复中的作用，从DNA甲基化、组蛋白修饰及蛋白翻译等方面探索其调控Notch1表达机制，拓宽人们对Notch1信号通路的认识，深入解析肝静脉闭塞病中肝修复的机理，为临床多种肝损伤相关疾病的治疗提供新视角。

The hepatic veno-occlusive disease (HVOD) is the severe complication after bone marrow stem cell transplantation. The risk and the degree of HVOD is dependent on the repair of the hepatic cells. Notch1 signaling is one of the key signaling pathways in the reparation of the hepatic cells. Previous studies mainly focused on the regulation of the Notch1 downstream signaling pathway. However, the regulative mechanism of Notch1 itself expression is still unclear. The long non-coding RNAs provide a new view of the gene expression regulation. Our studies indicate that the lncRNA 0610009E02Rik displays sequence similarity to the Notch1. Importantly, both the expression of the 0610009E02Rik and Notch1 is dawnregulated at the same time and display positive correlation in the hepatic cells which are obtained from bone marrow stem cell transplantation caused liver damaged mice models. All these results suggest that the lncRNA 0610009E02Rik is a positive regulator of Notch1 which expression has significantly effect on the reparation of the hepatic cells. In the project, we plan to elucidate the roles of the lncRNA 0610009E02Rik in the reparation of the hepatic cells and the regulative mechanisms of Notch1 gene expression from the DNA methylation, histone modification and protein expression level in the in vivo and in vitro hepatic cells damaged models. If successful, this study will broaden our vision on the acknowledgements of the Notch1 signaling and the repair mechanism of the hepatic cells in the HVOD.