We have made several significant progresses during the past year. We found the important roles of p53 in the differentiation of hESCs. We also identified that Nanog is a major coordinator of the self-renewal and proliferation of ES cells. We found that ATM is important to maintain the genetic stability of cells differentiated from hESCs. In addition, we identified an important phosphorylation event in activating ATM in hESCs. Finally, we identified a novel pathway to activate DNA damage in ES cells.