Dnmt3a^R878H/+ reduces proinflammatory transcriptional programs, specifically in HSCs. (A) Experimental design. (B) Principal component analysis of RNA-seq data from Dnmt3a^R878H/+ and Mx-Cre control cell types as well as C57BL/6 HSCs (n = 3 to 4 biological replicate mice per condition). (C) Volcano plots of differential gene expression in Dnmt3a^R878H/+ vs Mx-Cre control cell types. Significant differential expression (FDR <0.05) is indicated by colored dots; green dots (left side of each plot) represent genes lower in expression in Dnmt3a^R878H/+ vs control cells, and red dots (right side of each plot) represent genes higher in expression in Dnmt3a^R878H/+ vs control cells. (D) Gene signatures significantly enriched in Mx-Cre control (gray) or Dnmt3a^R878H/+ (navy) HSCs. (inset) Enrichment of a lipopolysaccharide-stimulated HSC signature¹⁶  in control vs Dnmt3a^R878H/+ HSCs. (E) Venn diagram of overlapping downregulated genes in mouse Dnmt3a^R878H/+ vs control HSCs with downregulated “Monocytic Priming” genes in human DNMT3A-F733S vs wild-type CD34⁺ cells.⁴¹ P value calculated using a hypergeometric test. (F) Gene signatures significantly enriched in accessible promoters of Mx-Cre control (gray) or Dnmt3a^R878H/+ (navy) HSCs.