Understanding the origins of stem cells in the embryo is essential for understanding how to guide formation of stem cell-derived tissues. Several stem cell-producing tissues exist in the early mouse embryo, which provides an ideal system for exploring mechanisms that guide stem cell development. In addition, stem cells can be artificially created by genetic reprogramming mature cells. We are interested in understanding how natural and reprogrammed stem cells compare. We use a variety of techniques, including mouse transgenics, bioinformatics, molecular biology, and confocal microscopy to examine the establishment and use of stem cells during normal development. From these studies, we hope to understand the molecular basis of cell fate and plasticity, as they relate to normal development and regenerative medicine.