Karin et al (2017) Molecular Systems Biology

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D Biphasic control of stem-cell expansion, where stem-cell expansion is low both at high and low concentrations of y. The system has a stable fixed point at the concentration of y where pr = 0.5 and an unstable fixed point at some lower concentration of y.

SED-ML simulation https://jjj.bio.vu.nl/models/experiments/karin2017_fig4d/simulate

C A mutated stem cell with a strong inactivation of the sensing of y has a growth advantage (differentiates less), and therefore, it invades the stem- cell population. As a result, both the stem-cell pool and the number of terminally differentiated cells increase.

SED-ML simulation https://jjj.bio.vu.nl/models/experiments/karin2017_fig4c/simulate

Mathematical simulation of a tamoxifen-induced conditional knock-in of a sixfold activating GCK mutant in beta cells. (C) The percentage of beta cells with mutated GCK increases to ~25% after 3 days, but then decreases and is eliminated after a few weeks. (D) Glucose levels initially decrease after the tamoxifen injection, but return to normal after a few weeks. Insets: Experimental results of Tornovsky-Babeay et al (2014).

SED-ML simulation https://jjj.bio.vu.nl/models/experiments/karin2017_fig2/simulate ...

C Trajectories of Z from different initial concentrations of cells (Z) (i) or y (ii) for the circuit of (B). The healthy concentration Z = ZST is reached regardless of initial concentration of Z, as long as it is nonzero, and regardless of the initial concentration of y.

SED-ML simulation https://jjj.bio.vu.nl/models/experiments/karin2017_fig1c/simulate

D An arrow marks the time when a mutant with a strong activation of the sensing of y arises (for the circuit depicted in B). This mutant has a selective advantage and takes over the population.

SED-ML simulation https://jjj.bio.vu.nl/models/experiments/karin2017_fig1d/simulate

G Trajectories of Z from different initial concentrations of Z (i) or y (ii) for the circuit depicted in (F). The healthy concentration Z = ZST is not reached for small values of Z (Z << ZST) or large values of y (y >> yUST).

SED-ML simulation https://jjj.bio.vu.nl/models/experiments/karin2017_fig1g/simulate

H The arrows mark the times when a mutant with a strong activation of the sensing of y arises (for the biphasic circuit depicted in F). This mutant has a selective disadvantage and is thus eliminated.

SED-ML simulation https://jjj.bio.vu.nl/models/experiments/karin2017_fig1h/simulate