Modeling of Regulatory Mechanisms for mESC Self-Renewal: Kinetic and Stochastic Approaches
Akberdin I.R., Ivanisenko N.V., Kazantsev F.V., Oschepkova E.A., Omelyanchuk N.A., Matushkin Yu.G., Afonnikov D.A.
Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia
Novosibirsk State University, Novosibirsk, Russia
Abstract. Analysis of the kinetic and stochastic models describing the dynamics of the core gene network for maintenance of pluripotency and differentiation of embryonic stem cells is represented. The core gene network was modified according to the latest experimental data on the regulation of Nanog expression. Analysis of the kinetic model showed that in the dynamics of the concentration changes as Nanog mRNA and protein could potentially exist oscillating mode, which may explains the experimentally observed Nanog heterogeneity in stem cell populations. Stochastic approach, in turn, allowed us to reveal a range of parameters, in which there are two possible system states as the result of stochastic fluctuations: the high and low levels of expression of Oct4, Sox2 and Nanog. It is possible to accidentally switch from one state to another that may also be one of the mechanisms of the Nanog heterogeneity.
Key words: pluripotency, differentiation, gene expression, Nanog heterogeneity, mathematical modeling.