Elevated NFκB activity in the niche is sufficient to dysregulate HSPC population dynamics. (A) Average cell counts in HSPC subpopulations from WT donors transplanted into WT (n = 6) and IκB⁻ (n = 4) recipients with individual data points overlaid. (B) ODE model parameter fits to average cell counts, in which differentiation rate and branching ratio for ST-HSCs and the rate parameters for each MPP population are allowed to vary between IκB⁻ and WT recipients. Formula for line of best fit specified for MPP parameters. (C) Transplanted HSPC scRNA-seq data projected into same gene expression space as native HSPC PCA with cells colored by genotype of recipient. (D) Ratio of IκB⁻ to WT recipient HSPC density over pseudotime (left) estimated 1000 times to reflect uncertainty in lineage assignments; solid line indicates median and shaded region covers minimum to maximum value. Top model fits (center) obtained for 1000 optimization runs of the PDE-based cell population dynamics model and respective normalized RMSD values (right). (E) Difference in branching-ratio (left) and lineage developmental-flux functions (right) between IκB⁻ and WT recipient given by parameters underlying model fits. Error bars and shaded regions denote range. (F) Difference in branching ratio (left) and average difference of developmental-flux functions in early (br.pt to 0.5) progenitor lineages (right) for model fits with different values for the branch-point. Lines connect median values, and error bars denote maximum/minimum values across 500 fits.