Document Detail


Soluble Jagged-1 is able to inhibit the function of its multivalent form to induce hematopoietic stem cell self-renewal in a surrogate in vitro assay.
MedLine Citation:
PMID:  14742638     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Stem cells reside in customized microenvironments (niches) that contribute to their unique ability to divide asymmetrically to give rise to self and to a daughter cell with distinct properties. Notch receptors and their ligands are highly conserved and have been shown to regulate cell-fate decisions in multiple developmental systems through local cell interactions. To assess whether Notch signaling may regulate hematopoiesis to maintain cells in an immature state, we examined the functional role of the recombinant, secreted form of the Notch ligand Jagged-1 during mouse hematopoietic stem cell (HSC) and progenitor cell proliferation and maturation. We found that ligand immobilization on stromal layer or on Sepharose-4B beads is required for the induction of self-renewing divisions of days 28-35 cobblestone area-forming cell. The free, soluble Jagged-1, however, has a dominant-negative effect on self-renewal in the stem-cell compartment. In contrast, free as well as immobilized Jagged-1 promotes growth factor-induced colony formation of committed hematopoietic progenitor cells. Therefore, we propose that differences in Jagged-1 presentation and developmental stage of the Notch receptor-bearing cells influence Notch ligand-binding results toward activation or inhibition of downstream signaling. Moreover, these results suggest potential clinical use of recombinant Notch ligands for expanding human HSC populations in vitro.
Authors:
Virág Vas; László Szilágyi; Katalin Pálóczi; Ferenc Uher
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-01-23
Journal Detail:
Title:  Journal of leukocyte biology     Volume:  75     ISSN:  0741-5400     ISO Abbreviation:  J. Leukoc. Biol.     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-03-31     Completed Date:  2004-05-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8405628     Medline TA:  J Leukoc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  714-20     Citation Subset:  IM    
Affiliation:
Stem Cell Biology, National Medical Center, Budapest, Hungary.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium-Binding Proteins
Cell Differentiation / drug effects,  physiology*
Cell Division / drug effects,  genetics
Cell Survival / drug effects,  genetics
Cells, Cultured
Female
Growth Substances / pharmacology
Hematopoiesis / drug effects,  genetics*
Hematopoietic Cell Growth Factors / metabolism,  pharmacology
Hematopoietic Stem Cell Transplantation / methods
Hematopoietic Stem Cells / drug effects,  metabolism*
Intercellular Signaling Peptides and Proteins
Male
Membrane Proteins
Mice
Mice, Inbred C57BL
Proteins / genetics,  metabolism*,  pharmacology
Receptor, Notch1
Receptors, Cell Surface / drug effects,  metabolism*
Signal Transduction / drug effects,  genetics
Transcription Factors*
Chemical
Reg. No./Substance:
0/Calcium-Binding Proteins; 0/Growth Substances; 0/Hematopoietic Cell Growth Factors; 0/Intercellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/Notch1 protein, mouse; 0/Proteins; 0/Receptor, Notch1; 0/Receptors, Cell Surface; 0/Transcription Factors; 134324-36-0/Serrate proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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