PBs unique erythroid/megakaryocyte–biased differentiation output becomes imbalanced with age and disease. (A) Ratio between BM- and spleen (SPL)-type identity scores in PB HSCs/MPPs according to age group. Notches indicate the 95% confidence interval of the median (middle line). (B) Frequencies of phenotypic HSCs/MPPs (CD19^–CD34⁺CD38^–CD45RA^–) in PB mononuclear cells (MNCs) by age group (n = 27, same data as in supplemental Figure 1B). (C) Percentage of colonies generated by single-cell–sorted phenotypic HSCs/MPPs from nonmobilized PB (same as in Figure 6C), grouped by age: <35 years, n = 942 single cells from 9 independent PBs; >60 years, n = 700 single cells from 8 independent PBs. (D) Median size of all My colonies (My, left) and all erythroid colonies (Ery, right) generated from nonmobilized PB HSCs/MPPs, grouped according to age as in panel C. (E) Volcano plot showing selected genes differentially expressed (false discovery rate <0.05) in Ery progenitors (cluster 8) of PB donors aged <35 years and aged >60 years. (F) Percentage of colonies generated by single-cell sorted phenotypic HSCs/MPPs from nonmobilized PB of healthy individuals (n = 445 cells, 5 individuals) and patients with ET (n = 349 cells, 5 individuals) over 5 experiments. (G) Percentage of colonies generated by single-cell sorted phenotypic HSCs/MPPs from nonmobilized PB of healthy individuals (same as in panel F) and patients with β-thalassemia (b-thal) (n = 271 cells, 3 individuals) over 3 experiments. Data in panels B, C, D, F, and G are given as mean ± standard deviation. Two-tailed Mann-Whitney U test. Undiff, undifferentiated; Meg, megakaryocyte; NK, natural killer; ns, not significant; Undiff, undifferentiated.