Our CIRM funded project have provided strong evidence suggesting miRNAs, and in a broader perspective, non-coding RNAs, as essential gene regulators in the self-renewal and pluripotency of embryonic stem cells. Consistently, these ncRNAs play an important role in the generation of induced pluripotent stem cells (iPSCs). Using expression studies, functional screening and candidate approaches, we have identified and characterized the roles of multiple miRNAs and long ncRNAs (lncRNAs) in regulating the self-renewal and differentiation of pluripotent stem cells. These non-coding RNAs are essential component of a regulatory network that regulate stem cell cell fate potential, self-renewal and differentiation potential. In the past 6 years being funded by CIRM, our team identified miRNAs/ncRNAs that enhance/suppress the self-renewal of pluripotent stem cells, and those that expand/restrict the differentiation potential of pluriptotent stem cells. These findings have revealed novel regulators of pluripotent stem cell biology, and pave the way to develop new diagnostic tools and therapeutical agent.