Hematopoietic stem cells (HSCs) exist as rare populations within blood-forming tissues that both self-renew and generate all blood cell lineages for life. HSCs have been isolated to relative purity in humans and mice, leading to a general understanding of their cellular and functional properties. Relatively little is known, however, regarding the genetic program underlying the embryonic formation and subsequent maintenance of HSC fate. The emergence of zebrafish as a model system has introduced unbiased genetic approaches, such as forward genetic screens and high-throughput expression screens, to the study of vertebrate blood cell formation. Fluorescent transgenesis technology combined with the external fertilization and transparency of zebrafish embryos allows early events in HSC specification, maintenance, and differentiation to be easily observed. Collectively, we are utilizing these advantages to image, fate map, and interrogate genetically the earliest embryonic blood-forming cells. This has helped address many long-standing questions in the development of the immune system, including the direct demonstration of HSC emergence from the transdifferentiation of aortic endothelium, and the demonstration of the importance of neighboring tissues in the instruction of HSC fate.
We are performing forward genetic and high-throughput expression screens to identify new gene functions in vertebrate stem cells. Novel genes that regulate HSC development, self-renewal, or lineage commitment will subsequently be examined for similar roles in mammalian systems. Despite decades of efforts, it is not yet possible to instruct HSC fate in vitro from pluripotent precursors. We hope that discovery of factors required to specify HSCs in the embryo will ultimately be useful in advancing this important goal of regenerative medicine.
David Traver received his Ph.D. in immunology from Stanford University where he received the McDevitt Prize for best thesis. He then completed postdoctoral studies at Harvard University as a fellow of the Irvington Institute. Since joining UCSD in 2004, he has received a Young Investigator Award from the Beckman Foundation, a Scholar Award from the American Society of Hematology and a New Faculty Award from the California Institute for Regenerative Medicine.