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Modèle de réseaux de contrôle de la prolifération cellulaire : application à la simulation de l'homéostasie d'un tissu épithélial stratifié en 2D

Didier Morel 1
1 RFMQ
TIMC - Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525
Abstract : The mechanisms controlling the homeostasis in a normal stratified epithelium are still not clear in vivo though many of them are now well characterised in vitro. Neither are the modifications of these controls misleading cells into a pathological behaviour. Computer simulation represents a powerful tool to investigate the complex field of cell proliferation regulation network. It provides huge computation capabilities to test hypotheses about redundant pathways and feedback loops that are now thought to be involved in cell growth and proliferation controls. Our approach develops a spatial representation of cells in 2D using the Voronoi graph and a model of cell growth, proliferation, differentiation and death controls. The Voronoi graph associates a polygon to every cell and the set of these polygons defines the tissue architecture. The model for cell growth, proliferation, differentiation and death regulation network includes intracellular (cyclins, Cyclin Dependent Kinases, Rb, CDKs inhibitors) and extracellular controls (growth and differentiation factors, integrins). This model, which integrates the spatial representation of cells, permits a quantitative modulation of the extracellular signals as a function of the cell neighbourhood during time dependent simulations. Thus, the characterisation of the modelled cells as Stem, Transit Amplifying or Committed cells is determined according to their molecular status (e.g. which protein is expressed, active, inhibited, etc...) at a given time. Our results show the role of CDK inhibitors (p15 and mainly p27) and of the ratio of growth and differentiation factors receptors in the G1 to S phase control. The 2D simulations illustrate the influence of the microenvironment and the patterning of stem cells on cell proliferation in basal layers of stratified epithelia and of differential adherence in keratinocytes differentiation and related upward migration.
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https://tel.archives-ouvertes.fr/tel-00004693
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Submitted on : Monday, February 16, 2004 - 5:09:25 PM
Last modification on : Thursday, November 19, 2020 - 3:56:07 PM
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Didier Morel. Modèle de réseaux de contrôle de la prolifération cellulaire : application à la simulation de l'homéostasie d'un tissu épithélial stratifié en 2D. Autre [q-bio.OT]. Université Joseph-Fourier - Grenoble I, 2001. Français. ⟨tel-00004693⟩

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