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J Exp Med. 2000 Nov 6;192(9):1365-72.

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

Author information

  • 1John P. Robarts Research Institute, Developmental Stem Cell Biology, and the Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario, Canada.

Abstract

The Notch ligand, Jagged-1, plays an essential role in tissue formation during embryonic development of primitive organisms. However, little is known regarding the role of Jagged-1 in the regulation of tissue-specific stem cells or its function in humans. Here, we show that uncommitted human hematopoietic cells and cells that comprise the putative blood stem cell microenvironment express Jagged-1 and the Notch receptors. Addition of a soluble form 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 immunodeficient mice revealed that human (h)Jagged-1 induces the survival and expansion of human stem cells capable of pluripotent repopulating capacity. Our findings demonstrate that hJagged-1 represents a novel growth factor of human stem cells, thereby providing an opportunity for the clinical utility of Notch ligands in the expansion of primitive cells capable of hematopoietic reconstitution.

PMID:
11067884
[PubMed - indexed for MEDLINE]
PMCID:
PMC2193352
Free PMC Article

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