The Journal of Experimental Medicine
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Published online 6 November 2000.
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© The Rockefeller University Press, 0022-1007/2000/11/1365/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 9, November 6, 2000 1365-1372

Brief Definitive Report

The Notch Ligand Jagged-1 Represents a Novel Growth Factor of Human Hematopoietic Stem Cells

Frances N. Karanua, Barbara Murdocha, Lisa Gallachera, Dongmei M. Wua, Masahide Koremotob, Seiji Sakanob, and Mickie Bhatiaa

a From The John P. Robarts Research Institute, Developmental Stem Cell Biology, and the Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario, Canada N6A 5K8
b The Second Research Department, Central Technology Laboratory, Asahi Chemical Industry Company, Limited, Shizuoka 416, Japan
The John P. Robarts Research Institute, Developmental Stem Cell Biology, 100 Perth Dr., London, Ontario, Canada N6A 5K8.519-663-3789519-663-5777 Ext. 34166

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.

Key Words: hematopoiesis • Jagged-1 • Notch • stem cells • development

© 2000 The Rockefeller University Press


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