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

doi:10.1084/jem.192.9.1365

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 Reports

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

Frances N. Karanu^a, Barbara Murdoch^a, Lisa Gallacher^a, Dongmei M. Wu^a, Masahide Koremoto^b, Seiji Sakano^b, and Mickie Bhatia^a
^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

Correspondence to: Mickie Bhatia, The John P. Robarts Research Institute, Developmental Stem Cell Biology, 100 Perth Dr., London, Ontario, Canada N6A 5K8. Tel:519-663-5777 Ext. 34166 Fax:519-663-3789

The Notch ligand, Jagged-1, plays an essential role in tissueformation during embryonic development of primitive organisms.However, little is known regarding the role of Jagged-1 in theregulation of tissue-specific stem cells or its function inhumans. Here, we show that uncommitted human hematopoietic cellsand cells that comprise the putative blood stem cell microenvironmentexpress Jagged-1 and the Notch receptors. Addition of a solubleform of human Jagged-1 to cultures of purified primitive humanblood cells had modest effects in augmenting cytokine-inducedproliferation of progenitors. However, intravenous transplantationof cultured cells into immunodeficient mice revealed that human(h)Jagged-1 induces the survival and expansion of human stemcells capable of pluripotent repopulating capacity. Our findingsdemonstrate that hJagged-1 represents a novel growth factorof human stem cells, thereby providing an opportunity for theclinical utility of Notch ligands in the expansion of primitivecells capable of hematopoietic reconstitution.

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

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