Figure 1.
Bias in HSC differentiation is insufficient to explain altered MPP populations. (A) Average HSPC subpopulation counts in IκB− (n = 10) vs WT (n = 12) with individual data points overlaid. (B) Schematic of ODE model of early hematopoiesis. (C) Regions of feasible/infeasible observations under a model that only permits the rate and differentiation bias of ST-HSCs to vary between WT and IκB− (top). The MPP rates of differentiation and net proliferation are the same between WT and IκB− for these analyses. Mean values collapsing MPP subpopulations (assuming common rates of differentiation and net proliferation across the 3 MPP subpopulations) is infeasible (middle). Mean values allowing distinct rates for each MPP subpopulation (that are then equivalent across experimental conditions) is feasible (line connecting values passes through feasible region) (bottom). (D) HSPC subpopulation cell-count ratios between IκB− and WT. Each IκB− animal was compared with each WT animal resulting in 120 sets of data points. Gray lines connect cell-count ratios originating from a single IκB− and WT pair. (E) Scatterplot of 120 observations on feasibility map (left) with common rates across MPPs. Only 24 (gray) are feasible. Most have an increase in IκB− MPPs that exceeds what is permissible (red). Allowing for measurement error, a relative error rate of nearly 40% is needed to account for all data under the restricted model (right). (F) Scatterplot of 120 observations on feasibility map (left) with distinct rates across MPPs; 64 (gray) are feasible and a relative error rate near 27% is needed to account for all data (right). (G) Parameter fits to the average cell counts for a model where ST-HSC differentiation and branching ratio is allowed to vary between IκB− and WT, as well as the rate parameters for each MPP population. Formula for line of best fit specified for MPP parameters. (H) Top 10% of parameter fits in (G) ordered by smallest total difference (absolute value of the logarithm of ratios) between IκB− and WT parameters (p).

Bias in HSC differentiation is insufficient to explain altered MPP populations. (A) Average HSPC subpopulation counts in IκB− (n = 10) vs WT (n = 12) with individual data points overlaid. (B) Schematic of ODE model of early hematopoiesis. (C) Regions of feasible/infeasible observations under a model that only permits the rate and differentiation bias of ST-HSCs to vary between WT and IκB− (top). The MPP rates of differentiation and net proliferation are the same between WT and IκB− for these analyses. Mean values collapsing MPP subpopulations (assuming common rates of differentiation and net proliferation across the 3 MPP subpopulations) is infeasible (middle). Mean values allowing distinct rates for each MPP subpopulation (that are then equivalent across experimental conditions) is feasible (line connecting values passes through feasible region) (bottom). (D) HSPC subpopulation cell-count ratios between IκB− and WT. Each IκB− animal was compared with each WT animal resulting in 120 sets of data points. Gray lines connect cell-count ratios originating from a single IκB− and WT pair. (E) Scatterplot of 120 observations on feasibility map (left) with common rates across MPPs. Only 24 (gray) are feasible. Most have an increase in IκB− MPPs that exceeds what is permissible (red). Allowing for measurement error, a relative error rate of nearly 40% is needed to account for all data under the restricted model (right). (F) Scatterplot of 120 observations on feasibility map (left) with distinct rates across MPPs; 64 (gray) are feasible and a relative error rate near 27% is needed to account for all data (right). (G) Parameter fits to the average cell counts for a model where ST-HSC differentiation and branching ratio is allowed to vary between IκB− and WT, as well as the rate parameters for each MPP population. Formula for line of best fit specified for MPP parameters. (H) Top 10% of parameter fits in (G) ordered by smallest total difference (absolute value of the logarithm of ratios) between IκB− and WT parameters (p).

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