Aged murine HSPCs show evidence of myeloid-primed progenitor expansion. (A) Average cell counts in HSPC subpopulations from young (n = 12) and old (n = 5) mice with individual data points overlaid. (B) HSPC scRNA-seq data from young and old mice projected into same gene expression space as native HSPC PCA with cells colored by age. (C) Expression of Nfkbia in old vs young HSPCs. Italicized number is P value given by Wilcoxon rank-sum test. (D) Ratio of old to young 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 old and young mice given by parameters underlying model fits. Error bars and shaded regions denote range. (F) Difference in branching ratio (top) and average difference of developmental-flux functions in early (branch-point to 0.5) progenitor lineages (bottom) for model fits with different values of the branch-point. Lines connect median values and error bars denote maximum/minimum values across 500 fits. (G) Expression of Cebpa and Ikzf1 along the HSC lineage (left) and expression of Myc and c-Myc response gene, Cdk4, along the MyP lineage (right) in old vs young HSPCs. Lines in G are NB-GAM fits, shaded regions are 95% confidence intervals, and transparent points are individual cell data. Italicized numbers are P values and degrees of freedom used for NB-GAM fits specified by k.