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Prepublished online as a Blood First Edition Paper on October 31, 2002; DOI 10.1182/blood-2002-06-1862. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-06-1862v1 101/5/1784    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Varnum-Finney, B. Articles by Bernstein, I. D. Search for Related Content PubMed PubMed Citation Articles by Varnum-Finney, B. Articles by Bernstein, I. D. Related Collections Hematopoiesis and Stem Cells Transplantation Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 March 2003, Vol. 101, No. 5, pp. 1784-1789 HEMATOPOIESIS Combined effects of Notch signaling and cytokines induce a multiple log increase in precursors with lymphoid and myeloid reconstituting ability Barbara Varnum-Finney, Carolyn Brashem-Stein, and Irwin D. Bernstein From the Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and the Department of Pediatrics, University of Washington, Seattle. We investigated whether combined signaling induced by engineered Notch ligands and hematopoietic growth factors influences hematopoietic stem-cell differentiation. We show that incubation of murine marrow precursors with Delta1ext-IgG, a Notch ligand consisting of the Delta1 extracellular domain fused to the Fc portion of human immunoglobulin G1 (IgG1), and growth factors stem cell factor (SCF), interleukin 6 (IL-6), IL-11, and Flt3-l inhibited myeloid differentiation and promoted a several-log increase in the number of precursors capable of short-term lymphoid and myeloid repopulation. Addition of IL7 promoted early T-cell development, whereas addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) led to terminal myeloid differentiation. These results support a role for combinatorial effects by Notch and cytokine-induced signaling pathways in regulating hematopoietic cell fate and suggest the usefulness of Notch ligand in increasing hematopoietic precursor numbers for clinical stem-cell transplantation. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Abdel-Azim, Y. Zhu, R. Hollis, X. Wang, S. Ge, Q.-L. Hao, G. Smbatyan, D. B. Kohn, M. Rosol, and G. M. Crooks Expansion of multipotent and lymphoid-committed human progenitors through intracellular dimerization of Mpl Blood, April 15, 2008; 111(8): 4064 - 4074. [Abstract] [Full Text] [PDF] B. Varnum-Finney, M. H. Dallas, K. Kato, and I. D. Bernstein Notch target Hes5 ensures appropriate Notch induced T- versus B-cell choices in the thymus Blood, March 1, 2008; 111(5): 2615 - 2620. [Abstract] [Full Text] [PDF] U. Blank, G. Karlsson, and S. 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