Fig. 3

iPSCs with JAK2 V617F fail to recapitulate disease-associated changes. a, b Scatter plots showing mean DNAm beta values of a) wild type (WT) versus JAK2 V617F heterozygous (het) iPSCs, and b) WT versus JAK2 V617F homozygous (hom) iPSCs. The numbers of CpGs with > 20% DNAm difference are indicated, but none reached statistical significance. c, d To determine if DNAm changes in PMF patients with JAK2 V617F are reflected in iPSCs with or without JAK2 V617F, we focused on CpGs that were significantly differentially methylated in JAK2 V617F PMF versus healthy control (from Fig. 2a). Average DNAm changes were then analyzed in these CpGs in iPSCs with either c) WT versus heterozygous JAK2 V617F, or d) WT versus homozygous JAK2 V617F. e, f Following differentiation of iPSC lines into hematopoietic progenitor cells (iHPCs), scatter plots depict mean DNAm beta values for e) WT versus JAK2 V617F heterozygous iHPCs, and f) WT versus JAK2 V617F homozygous iHPCs (none of the CpGs reached statistical significance). Gray numbers indicate all CpGs exceeding the mean DNAm difference > 20%, irrespective of statistical significance. g, h The CpGs with significant differences in JAK2 V617F PMF versus healthy controls were reanalyzed in iHPCs: g) heterozygous and h) homozygous JAK2 V617F iHPCs exhibited an overall decrease in DNAm at CpGs that gained or lost methylation in JAK2 V617F PMF. Statistical significance was evaluated using one-way ANOVA