Linked Life Data

17761753

Source:http://linkedlifedata.com/resource/pubmed/id/17761753

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2007-12-17
pubmed:abstractText
The activation of Notch signaling in neural crest stem cells (NCSCs) results in the rapid loss of neurogenic potential and differentiation into glia. We now show that the attenuation of endogenous Notch signaling within expanding NCSC clones by the Notch ligand soluble Jagged1 (sJ1), maintains NCSCs in a clonal self-renewing state in vitro without affecting their sensitivity to instructive differentiation signals observed previously during NCSC self-renewal. sJ1 functions as a competitive inhibitor of Notch signaling to modulate endogenous cell-cell communication to levels sufficient to inhibit neural differentiation but insufficient to instruct gliogenic differentiation. Attenuated Notch signaling promotes the induction and nonclassic release of fibroblast growth factor 1 (FGF1). The functions of sJ1 and FGF1 signaling are complementary, as abrogation of FGF signaling diminishes the ability of sJ1 to promote NCSC expansion, yet the secondary NCSCs maintain the dosage sensitivity of the founder. These results validate and build upon previous studies on the role of Notch signaling in stem cell self-renewal and suggest that the differentiation bias or self-renewal potential of NCSCs is intrinsically linked to the level of endogenous Notch signaling. This should provide a unique opportunity for the expansion of NCSCs ex vivo without altering their differentiation bias for clinical cell replacement or transplant strategies in tissue repair. Disclosure of potential conflicts of interest is found at the end of this article.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1549-4918
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3133-42
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Soluble Jagged1 attenuates lateral inhibition, allowing for the clonal expansion of neural crest stem cells.
pubmed:affiliation
Interdisciplinary Program in Molecular Genetics and Cell Biology, University of Maine, Orono, Maine, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural