The notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells

The Notch ligand, Jagged-1, plays an essential role in tissue formation dur ing embryonic development of primitive organisms. However, Little is known regarding the role of Jagged-1 in the regulation of tissue-specific stem ce lls or its function in humans. Here, we show that uncommitted human hematop oietic cells and cells that comprise the putative blood stem cell microenvi ronment express Jagged-1 and the Notch receptors. Addition of a soluble for m of human Jagged-1 to cultures of purified primitive human blood cells had modest effects in augmenting cytokine-induced proliferation of progenitors . However, intravenous transplantation of cultured cells into immunodefcien t mice revealed that human (h)Jagged-l induces the survival and expansion o f human stem cells capable of pluripotent repopulating capacity. Our findin gs demonstrate that hJagged-1 represents a novel growth factor of human ste m cells, thereby providing an opportunity for the clinical utility of Notch ligands in the expansion of primitive cells capable of hematopoietic recon stitution.