The world of small non-coding RNAs (ncRNA) is continuously expanding, reinforcing the biological importance of these species in both development and disease. Over the past year, our efforts funded by CIRM has been focused on studying the roles of these small ncRNAs in regulating stem cell self-renewal and differentiation. miRNAs are a class of novel, small ncRNAs that negatively regulate global gene expression at posttranscriptional level. Using expression studies, we have characterized the miRNA expression profiles in both ES cells and induced pluripotent stem cells (iPS cells). This effort led to the identification of multiple miRNAs whose levels of expression are either enriched or depleted during stem cell reprogramming. A key finding of the previous funding period is the identification of a novel miRNA, Esdmir-1, whose loss-of-function significantly promotes the reprogramming of iPS cells. This is an important finding, not only does it set up a paradigm for our future studies, it also provides an attractive methodology to improve iPS reprogramming in human. Our future effort in the next funding period (year 2) will be focused on completing the studies on Esdmir-1, evaluating the functions of additional candidate miRNAs in stem cell self-renewal and differentiation and identifying novel ncRNAs that regulate stem cell biology.