Individual mouse embryonic stem cells have been found to exhibit highly variable differentiation responses under the same environmental conditions. Recent experimatal evidence suggest that the noisy cyclic expression of Hes1 and its downstream genes are responsible for this, but the mechanism underlying this variability in expression is not well understood.
Together with Mark Chaplain’s group, we have recenly published a new paper in Journal of the Royal Society Interface, where we propose a spatial stochastic model of the Hes1 regulatory network. Simulations of this model with URDME suggest that the Hes1 oscillations will intrinsically give rise to broad period distributions, and hence very heterogenous cell popuations with respect to Hes1 expression. Our work suggests a simple mechanism to explain the observations that cells that were sorted according to high or low expression of Hes1 relaxed back to a heterogenous mixture of Hes1 expression. We also propose experiments to control the precise differentiation response using drug treatment.
