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Spatial stochastic modelling of the Hes1 gene regulatory network: intrinsic noise can explain heterogeneity in embryonic stem cell differentiation

Individual mouse embryonic stem cells have been found to exhibit highly variable differentiation responses under the same environmental conditions. The noisy cyclic expression of Hes1 and its downstream genes are known to be responsible for this, but the mechanism underlying this variability in expr...

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Detalles Bibliográficos
Autores principales: Sturrock, Marc, Hellander, Andreas, Matzavinos, Anastasios, Chaplain, Mark A. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565746/
https://www.ncbi.nlm.nih.gov/pubmed/23325756
http://dx.doi.org/10.1098/rsif.2012.0988
Descripción
Sumario:Individual mouse embryonic stem cells have been found to exhibit highly variable differentiation responses under the same environmental conditions. The noisy cyclic expression of Hes1 and its downstream genes are known to be responsible for this, but the mechanism underlying this variability in expression is not well understood. In this paper, we show that the observed experimental data and diverse differentiation responses can be explained by a spatial stochastic model of the Hes1 gene regulatory network. We also propose experiments to control the precise differentiation response using drug treatment.