Soluble Jagged1 Attenuates Lateral Inhibition, Allowing for the Clonal Expansion of Neural Crest Stem Cells
| Autor: | Maria F. Duarte, Joseph M. Verdi, Igor Prudovsky, George N. Nikopoulos, Thomas Maciag, Robert Friesel, Chris J. Kubu, Stephen Bellum |
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| Rok vydání: | 2007 |
| Předmět: |
Notch signaling pathway
Biology Fibroblast growth factor Cell therapy Animals Humans Serrate-Jagged Proteins Receptor Notch1 Cells Cultured Cell Proliferation Neurons Stem Cells Calcium-Binding Proteins Membrane Proteins Neural crest Cell Differentiation Neural Inhibition Cell Biology FGF1 Clone Cells Rats Cell biology Solubility Neural Crest Hes3 signaling axis Intercellular Signaling Peptides and Proteins Molecular Medicine Stem cell Developmental biology Jagged-1 Protein Signal Transduction Developmental Biology |
| Zdroj: | Stem Cells. 25:3133-3142 |
| ISSN: | 1549-4918 1066-5099 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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