Human homologs of delta-1 and delta-4 function as mitogenic regulators of primitive human hematopoietic cells

Delta mediated Notch signaling controls cell fate decisions during invertebrate and murine development. However, in the human, functional roles for Delta have yet to be described. Here we report the characterization of Delta-1 and Delta-4 in the human. Human Delta-4 was found to be expressed in a wide range of adult and fetal tissues, including active sites of hematopoiesis. Subsets of immature hematopoietic cells, along with stromal and endothelial cells that support hematopoiesis, were shown to express Notch and both Delta1 and 4. Soluble forms of hDelta-1 and 4 proteins were able to augment the proliferation of primitive human hematopoietic progenitors in vitro. Intravenous transplantation of treated cultures into immune deficient mice revealed that hDelta-1 is capable of expanding pluripotent human hematopoietic repopulating cells detected in vivo. Our study provides evidence for a role of Deltas in the human which function as mitogenic regulators of hematopoietic stem cells.