To fulfill the promise of pluripotent stem cells, both embryonic and induced pluripotent stem cells, it is essential to fully understand their properties and how those properties can be manipulated to make any cell in the human body. The best way to reach that goal is to understand the relationships between these cells that grow in a culture dish in the laboratory and the equivalent cells in the developing embryo. As working with human embryos comes with many ethical concerns, an important alternative is the mouse model. Indeed, much of what we have learned in the mouse model has later been confirmed in human. Therefore, we use a combination of the mouse model and human cells to dissect the molecular basis of stem cell function and differentiation toward adult tissues. In particular, we have been focusing on a class of molecules called small RNAs that were only discovered in the 1990s and became widely appreciated in the past decade. There are several classes of these small RNAs, two of which our lab focuses on, microRNAs and endogenous siRNAs. We have found these small RNAs are essential for normal mammalian development and growth and differentiation of stem cells. In the past year, we have been following up exciting roles for endogenous siRNAs in the development of the egg. These small RNAs are essential for the growth of a healthy egg by controlling accurate distribution of DNA. We also discovered that microRNA function is actively suppressed during this important time window. We have made headway into discovering the proteins responsible for this suppression. We believe these proteins will give us hints into how the egg prepares the genome to produce the cells that can replace any tissue in our body. MicroRNA first function at the time an embryo implants into the uterus of the mother. We have found that two groups of microRNAs are acting at this stage. We believe these specific microRNAs play essential roles in the transition from the cells that can make every tissue to a more specialized state where they can only make specific cells. To test this idea, we have made stem cells and mice that are deleted for these miRNAs to see how their loss influences developmental potential of the cell. Similarly, we are determining roles for endogenous siRNAs at these later stages of development by making mice where they have been removed. Together these results are giving new and important insights into the role of small RNAs in early embryonic development. This research is expected to enable to us to more easily manipulate cell fates to produce high quality cells that could be used to study diseases of many types as well as reintroduce healthy tissue into patients with degenerative diseases.