Figure 5.

SF3B1^K700E HSPCs have altered chromatin landscapes. (A) PCA based on accessibility of all peaks in the ATAC-seq atlas color-coded by SF3B1 mutation status and sign-coded by patient ID. (B) Heatmap showing the distance of the HSPCs from the indicated iPSC lines, based on pairwise Pearson correlation of their chromatin accessibility landscapes, color-coded by SF3B1 mutation status and patient ID. (C) Scatterplot showing the accessibility log₂fc and the adjusted P value of the differentially accessible peaks between SF3B1^K700E and SF3B1^WT iPSC-HSPCs per chromosome, color-coded by the adjusted P value. Each point represents a peak. (D) Cumulative distribution function (CDF) of the expression log₂fc of genes more accessible in SF3B1^K700E HSPCs, genes less accessible in SF3B1^K700E HSPCs, and all genes, showing that genes more accessible in SF3B1^K700E HSPCs are upregulated (Kolmogorov–Smirnov [KS] test, P = 1.17e-07) and genes less accessible in SF3B1^K700E HSPCs are downregulated (KS test, P = 3.13e-16) compared with background. (E) Scatterplot showing the log₂fc accessibility value of the differentially accessible peaks and the log₂fc expression value of the linked gene (genes for which P value could not be calculated were excluded). (F) Heatmap showing Pearson correlation values of normalized read counts for ATAC-seq peaks that overlap between the indicated iPSC-HSPCs and primary normal hematopoietic cell subpopulations (hematopoietic stem cells [HSC], multipotent progenitors [MPP], common myeloid progenitors [CMP], lymphoid-primed multipotent progenitors [LMPP], granulocyte- monocyte progenitors [GMP], megakaryocyte-erythrocyte progenitors [MEP], common lymphoid progenitors [CLP], monocytes [Mono], erythroid cells [Ery], natural killer cells [NK], and B cells) from Corces et al.³⁶