Studies on lncRNAs suggest an key role in development and cancer, however, no ISC-specific lncRNAs have been identified. Here I will study the role of lncRNAs in ISC development. I already identified lncRNAs that are enriched in ISCs and targets of Wnt pathway by analyzing RNA-sequencing (RNA-seq) and ChIP-seq from Lgr5 + ISCs (unpublished result). From this primary data set, I will find functional lncRNA candidates and define the action mechanisms of the lncRNAs. Lastly, I will elucidate the physiological function of the lncRNAs by generating knock-out mouse models. It has become evident that lincRNAs regulate multiple cellular functions including pluripotency, differentiation, and cell cycle. This project will, therefore, broaden our knowledge on adult stem cell biology revealing how lincRNAs play a role in self-renewal and differentiation of ISCs. At the same time, this project will extend our understanding of lincRNA biology by providing a comprehensive functional study in a physiologically relevant system. Furthermore, given that Lgr5+ ISCs are starting point of the formation of cancer stem cells and that colorectal cancer stem cells show a similar gene expression pattern with Lgr5+ ISCs, the defined lincRNAs might be used as diagnostic markers and therapeutic targets in cancer.