The genome integrity of pluripotent stem cells, which give rise to all the cell lineages including the germline, is of fundamental importance to both basic biology as well as biomedical application. However, it remains largely unclear whether and how the genetic stability of pluripotent stem cells and germline stem cells is properly coordinated with their cellular proliferation and differentiation programs. To better understand these issues, we are carrying out systematic and detailed characterization of DNA damage responses in mouse embryonic stem cells, germline stem cells and their differentiated progenies. Our research aims to understand the developmental stage and/or cellular context dependent control of genome stability and diversification in the germline stem cell cycle.