Hematopoietic or blood stem cells (HSCs) generate all red and white blood cells for the life of a vertebrate organism. HSCs are also the therapeutic elements of bone marrow transplant therapies used in the treatment of blood disorders, including leukemias and genetic disorders like sickle cell anemia. HSCs develop during embryonic development from endothelial cells that make up the floor of the dorsal aorta blood vessel. These cells transition into HSCs after receiving molecular signals/cues from neighboring cells. Understanding these signals/cues and the transcriptional programs regulated by them is biomedically important. The generation of patient tailored HSCs in vitro from the patient’s own adult induced pluripotent stem cells is a major biomedical objective that has potential to alleviate bone marrow transplant rejection and improve tools for gene therapy-based treatment of genetic blood disorders like sickle cell disease. However, to date it has not been possible to generate transplantable HSCs in vitro, most likely because the full set of developmental signals has not been identified. Thus, investigating the in vivo genetic and molecular control of HSC development is an important prerequisite to addressing these challenges.
The Damm laboratory works at the intersection of neural, blood and blood vessel development and takes advantage of the unique attributes of the zebrafish embryo model system to address biological questions related to the development of HSCs in the vertebrate embryo.