Dynamics of Stem Cells in Liver Homeostasis, Injury and Carcinogenesis

General aims of this thesis are:
1) to investigate the dynamics of LGR5 proliferative stem cells in homeostatis and injury of the liver, and to characterize the role of LGR5 stem cell in maintenance of the stem cell pool ex vivo
2) to demonstrate the existence and function of quiescent stem cells using the long-term label retaining assay
3) to investigate the interrelationship of the proliferative LGR5 stem cells and the quiescent stem cell during liver homeostasis and injury
4) to establish malignant organoid models from mouse primary liver tumors and demonstrate their applications in liver cancer research
5) to investigate the existence and function of liver cancer stem cells by adopting transgenic mouse model and 3D organoid model
6) to investigate whether normal LGR5 proliferative stem cells participate in the tumor progression and formation by using LGR5 lineage tracing mouse. The results provide a wealth of data on the action and function of the LGR5 stem cell compartment and other stem cell compartment in hepatic physiology and pathology