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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
Author(s) -
Vas Virág,
Szilágyi László,
Pálóczi Katalin,
Uher Ferenc
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1003462
Subject(s) - biology , microbiology and biotechnology , stem cell , haematopoiesis , progenitor cell , notch signaling pathway , stem cell factor , hematopoietic stem cell , stromal cell , immunology , signal transduction , cancer research
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.