Figure 4

Numerical simulations of proliferating and non-proliferating cells in the absence and presence of HIA and CTA treatment under different parameter settings. Simulations of the model show P versus t (bottom curve) and N versus t (top curve) in four cases. A. HIA and chemotherapy treatment are both absent (the control case). B. HIA is present and chemotherapy treatment in absent. C. HIA is absent and chemotherapy treatment is present. D. HIA and chemotherapy treatment are both present. In all four simulations m was increased from 0.1 to 1, θ₁ was decreased from 100 to 60, w was increased from 1 to 2, and θ₂ was decreased from 100 to 60. The increase in w reflects an increase in the sensitivity of the rate at which cells proliferate due to changes in CTA treatment. The increase in θ₁ reflects a decrease in the sensitivity of the rate at which cells proliferate due to changes in HIA administration. The decrease in θ₁ and θ₂ from 100 to 60 causes a response in stem cells due to CTA and HIA at lower levels of the HSC population. These changes in parameter values do not significantly alter the overall HSC levels as compared with Figure 3. Note that there is no change from Figure 3A to Figure 4A since in this case, HIA administration and CTA treatment are absent.