Research Paper Volume 6, Issue 12 pp 1033—1048

Stochastic modeling indicates that aging and somatic evolution in the hematopoietic system are driven by non-cell-autonomous processes

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Figure 6. Clonal dynamics in the simulated HSC pools under different parameters of mutation and micro-environmental DFEs. OVERLAP (left panels): % area of the plausible range of mutation parameters that allows age-dependent exponential clonal expansions under different stringencies (a minimum of 0.7, 0.8, or 0.9 shape match) of the expansions' match to the reference leukemia curve. ENV DFE – DFE imposed by microenvironment (explained in the text). EXPANSIONS (right panels): average magnitude of clonal expansions under different parameters of mutation and microenvironmental DFEs, measured as the % of pool occupied by the most successful clone at the end of the simulated life. (A) Comparison between mutation-alone (upper panels) and mutations + microenvironment (mutations + ENV) models (lower panels) under a stable adult HSC pool size of 11,000 cells; mutation DFE in the positive tail in all mutation + ENV conditions was set to 0%. (B) Same as A under different adult pool sizes and a slower cell cycling speed estimates (slow cycle); 11k->25k – the adult pool size increases over lifetime from 11,000 to 25,000 cells; mutation DFE in the positive tail in ALL conditions was set to 1% and ENV DFE in the positive tail was set to 0%. Numeric data is presented in Table S1.