Washington University in St. Louis (WU)
Our research program utilizes an in vitro differentiation model of embryonic stem (ES) cells and early mouse embryos to study the mechanisms by which blood (hematopoietic) and blood vessel (endothelial) cell lineage differentiation are regulated. So far we have shown that hematopoietic and endothelial cells develop from mesoderm via an intermediate progenitor known as the hemangioblast, which expresses Flk-1, a receptor tyrosine kinase, and Scl, a transcription factor. We are currently investigating signals that control the step-wise commitment from mesoderm to Flk-1 expressing mesoderm, from the Flk-1 expressing mesoderm to the hemangioblast, and from the hemangioblast to hematopoietic and endothelial cells. In addition, we are investigating transcriptional regulatory mechanisms involved in hemangioblast specification and differentiation. Our preliminary studies indicate that the hemangioblast gene expression pattern is similar to that of other stem cells, including hematopoietic, neural and embryonic. Our hope is to better understand regulatory mechanisms involved in stem cell renewal and differentiation. Ultimately, we want to apply this knowledge to modulate stem cell function and facilitate isolation of various progenitor/precursor cells for therapeutic purposes. Additionally, as embryonic signaling is often reactivated in disease states, we are currently testing a hypothesis whether signaling involved in embryonic hematopoiesis and vasculogenesis is reactivated in diseases. Such characterization will be critical for understanidng and controlling pathologic conditions, such as inflammation and tumor angiogenesis.