Since the cells tend to a final equilibrium in which the ����high P���� state is more likely than the ����low P���� phenotype and the conversion rate depends only on the noise level. This dynamics may be due to the suppression of the density sensing when the decision to change phenotype is predominantly cell autonomous. Next we examined the behaviour of the system with constant kinetic parameters and as a function of local cell GDC-0941 densityand phenotype-dependent noise and of intrinsic noise. As expected for a bistable system, when the two noise terms were low no conversion occurred and dS was close to zero. When the context dependent noise was high but the intrinsic noise was low the highP cells converted to ����low P���� easier than the opposite. This is illustrated on the Fig. 5 and Fig. 6B.This regime reproduced qualitatively the observations made on living cell cultures. As expected, ����low P���� cells were preferentially located in low-density regions and ����high P���� cells in high-density regions. The observed asymmetry of the PCI-32765 transformation rates was solely due to the double- dependence of the noise level because the specific regulation of the phenotype determination was identical in all cells and independent of the local cell density. When the intrinsic noise Nint was high and dominated over the effect of the Next we observed a dynamic regime with the ����highP����cells converting to ����low P���� slower than the opposite. Qualitatively, this behaviour is the opposite of that observed in normal living cell cultures and it was similar to that observed under the conditions when the local density weakly influenced the kinetic parameters of the phenotypic transition with constant intrinsic noise. In addition, this dynamics is reminiscent of a system where the rapid switch to one state and slow relaxation to the initial state was triggered by noise excitation without density sensing described by Kalmar et al.. Based on the simulations it is likely that the apparently paradoxical slow transformation of sorted ����low P���� compared to sorted ����high P���� cells is a logical consequence of the local densitysensing capacity and the fact that the experiment always starts with low initial cell density. The sensing of the local density may occur either by a specific mechanism that targets the activity of myogenic genes or by simply modulating the gene expression noise in a density- and phenotype-dependent way. Since our model provides only qualitative predictions, we cannot directly differentiate the two possibilities. The simulations suggest that if the capacity of the cells to sense local density is reduced the phenotypic transition of the ����low P���� cells into ����high P���� will be faster than the opposite.