Human homologues of Delta-1 and Delta-4 function as mitogenic regulators of primitive human hematopoietic cells

Delta-mediated Notch signaling controls cell fate decisions during inverteb rate and murine development. However, in the human, functional roles for De lta have yet to be described, This study reports the characterization of De lta-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 sites of hematopoiesis. Subsets of immature hematopoietic cells, along with stromal and endothelial cells that support hematopoiesis, were shown to express Notch and both Del ta-1 and Delta-4, Soluble forms of human Delta-1 (hDelta-1) and hDelta-4 pr oteins were able to augment the proliferation of primitive human hematopoie tic progenitors in vitro. Intravenous transplantation of treated cultures i nto immune-deficient mice revealed that hDelta-1 is capable of expanding pl uripotent human hematopoietic repopulating cells detected in vivo. This stu dy provides the first evidence for a role of Delta ligands as a mitogenic r egulator of primitive hematopoietic cells in the human. (Blood, 2001;97:196 0-1967) (C) 2001 by The American Society of Hematology.