Titre :
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Reversibility of the myogenic marker CD56 in human cells : a bistable expression dependent on stochastic fluctuations and spatial micro-environment
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contenu dans :
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Auteurs :
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4th International Congress of Myology, 4ème colloque international de Myologie (9-13 mai 2011; Lille (France)) ;
Stockholm D ;
Edom-Vovard F ;
Coutant S ;
Sanatine P ;
Corre C ;
Neildez-Nguyen TMA ;
Paldi A
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Type de document :
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Article
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Editeur :
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AFM-TELETHON, 2011
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Pages :
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p. 142
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Langues:
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Anglais
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Résumé :
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The Neural cell adhesion molecule (NCAM;CD56) is considered as a marker of myogenic cells committed to differentiation. It is commonly used for the enumeration of satellite cells and for the enrichment of myogenic cell population from muscle for cell therapy perspective. In this study we show that human primary mononuclear muscle cells spontaneously fluctuate between different states characterized by the either high or low expression of the muscle-specific cell surface molecule CD56 and by the corresponding high or low capacity to form myotubes. By the use of cell sorting and cell cloning, the reversibility of CD56 expression was demonstrated. Furthermore, using spatial distribution analysis of the cells in a growing population, we determined a correlation between CD56 expression level and the local density suggesting a strong influence of the microenvironment on the stability of this expression.We propose a model explaining such behavior based on a bistable expression of CD56 driven by cell-intrinsic fluctuations but also by collective cell-to-cell interactions. The cells switch their phenotype under the constraints imposed by the highly heterogeneous microenvironment created by their own collective movement. The cellular microenvironment contributes actively to the fluctuations by increasing the noise level in cells with a given phenotype and decreasing it in others. Importantly, the microenvironment is created by the cells themselves as a consequence of their motility that creates random cell interactions. In this way each cell contributes to put together its own microenvironment that in turn stimulates it to fluctuate between the phenotypes until the most appropriate phenotypic state with low noise is found. The resulting heterogeneous cell population is characterized by a dynamic equilibrium between "high CD56" and "low CD56" phenotype cells with distinct spatial distribution.
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