A central goal of our CIRM SEED proposal was to use innovative approaches to discover genes that control human embryonic stem cells, with the idea that this knowledge may lead to improved methods for growth and/or differentiation of human pluripotent stem cells in a clinical setting. In the past year we have continued to make significant progress on these efforts. We have found a factor that acts to turn other genes on or off and is active in embryonic stem cells. We have put a considerable amount of effort into optimizing methods to identify exactly what genes this factor controls. Our results show that this factor directly regulates pluripotency-associated genes. This is remarkable, since this factor had not to date been implicated in the regulation of pluripotency. These results put us in a position to characterize the function of this factor in embryonic stem cells in greater detail. In addition, we are applying knowledge gained from our studies to develop methods to enhance the ease with which human pluripotent stem cells are propagated. Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, are notoriously more difficult to grow than their mouse counterparts, and this has significantly hampered the ability to use existing human pluripotent stem cells to model disease. We have developed conditions that facilitate the propagation of human pluripotent stem cells in a state that resembles mouse ES cells, where they are easier to propagate and grow more rapidly. These findings, while preliminary, suggest that we have the opportunity to explore a transition of human pluripotent stem cells to a state that is easier to culture and manipulate genetically. Thus, the CIRM SEED award has allowed us to discover a novel regulator of pluripotency genes, and to develop conditions that may lead to improved culture and manipulation of human pluripotent stem cells.