Meeting Abstract
Through the decades of bone marrow transplantation research, understanding hematopoietic stem cell (HSC) activation and leukocyte mobilization into the bloodstream has been imperative to investigators trying to manipulate these mechanisms and control the production of blood cells from donors, known as hematopoiesis. The little skate (Leucoraja erinacea) may serve a unique role in these studies as it lacks an endosteal (i.e., composed of bone) hematopoietic niche, such as that housing mammalian bone marrow. While this compartmentalization is protective in mammals, it is an obstructive barrier for studies of transplantation immunology. L. erinacea possesses specialized tissues (the Leydig and epigonal organs), similar in function to mammalian bone marrow but uniquely composed of only the vascular niche; it is within these organs that HSC are maintained. While many molecular and cellular interactions modulate hematopoiesis, the chemokine receptor-ligand pair, CXCR4-CXCL12, is known to play a critical role in homing of HSC for cellular transplant engraftment, as well as maintenance of homeostasis in the bone marrow. Thus, inhibiting this connection with clinical agents, such as AMD3100, a CXCR4 antagonist, activates HSC. We have identified and annotated CXCR4 and CXCL12 expression in L. erinacea using genomic and transcriptomic sequence information from the North East Cyberinfrastructure Consortium, available at Skatebase.org. In addition, L. erinacea treated with AMD3100 exhibited significant leukocyte mobilization, as assessed by serological methods. Therefore, important implications exist for the L. erinacea model in studies of transplantation physiology and potential therapies for hematological diseases.
