PMID: identifiant
de la référence Pubmed : |
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 (16594731)  |
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| titre : |
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Notch promotes neural lineage entry by pluripotent embryonic stem cells. |
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| auteur(s) : |
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Sally Lowell1, Alexandra Benchoua1, 2, Barry Heavey1, Austin Smith ( ) 1, 3 |
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| laboratoire : |
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| résumé : |
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A central challenge in embryonic stem (ES) cell biology is to understand how to impose direction on primary lineage commitment. In basal culture conditions, the majority of ES cells convert asynchronously into neural cells. However, many cells resist differentiation and others adopt nonneural fates. Mosaic activation of the neural reporter Sox-green fluorescent protein suggests regulation by cell-cell interactions. We detected expression of Notch receptors and ligands in mouse ES cells and investigated the role of this pathway. Genetic manipulation to activate Notch constitutively does not alter the stem cell phenotype. However, upon withdrawal of self-renewal stimuli, differentiation is directed rapidly and exclusively into the neural lineage. Conversely, pharmacological or genetic interference with Notch signalling suppresses the neural fate choice. Notch promotion of neural commitment requires parallel signalling through the fibroblast growth factor receptor. Stromal cells expressing Notch ligand stimulate neural specification of human ES cells, indicating that this is a conserved pathway in pluripotent stem cells. These findings define an unexpected and decisive role for Notch in ES cell fate determination. Limiting activation of endogenous Notch results in heterogeneous lineage commitment. Manipulation of Notch signalling is therefore likely to be a key factor in taking command of ES cell lineage choice. |
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| domaine : |
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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1544-9173 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1371/journal.pbio.0040121 |
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| journal : |
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| Audience : |
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internationale |
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| date de publication : |
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05/2006 |
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date de publication
électronique : |
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11/04/2006 |
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| volume : |
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4 |
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| numéro : |
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5 |
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| page, identifiant, ... : |
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e121 |
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| Descripteur(s) MeSH : |
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Animals – Cell Differentiation – Cell Lineage – Cells – Cultured – Embryonic Stem Cells – Gene Expression Regulation – Humans – Mice – Neurons – Phenotype – Pluripotent Stem Cells – Receptors – Notch – Signal Transduction |
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| contrat, financement : |
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This research was funded by the Biotechnology and Biological Sciences Research Council and the Medical Research Council of the United Kingdom, by the European Union Framework VI Integrated Project EuroStemCell, and by a Wellcome Trust International Fellowship to SL. |
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