Loss of Ezh2 reprogrammed the transcriptional landscape of HSPCs. (A) Gene expression alterations associated with disease progression. GSEA was performed using the microarray analysis data of WT and Ezh2^Δ/Δ LSK cells from early and late time points after the deletion of Ezh2 (3 and 9-12 months, respectively). LSK cells were also collected individually from MDS (10F14 and 11F2), MDS/MPN (11F5), and MDS/MPN_TC mice (10F7) ∼10 months after the deletion of Ezh2. The NES from the gene expression profiles of LSK cells derived from GSEA is shown as a number in each cell. The NOM P value and FDR are shown below NES. Red and blue colors represent positive (upregulated in the given genotype relative to WT) and negative (upregulated in WT relative to the given genotype) enrichment, respectively. (B) Gene set enrichment plots for the bivalent gene set in HSCs in panel A comparing Ezh2^Δ/Δ LSK cells to WT LSK cells 3 and 9 to 12 months after the deletion of Ezh2.