Fig. 4: HSF1 regulated genes are involved in multifaceted LSC functions.

a–c RNA-seq analysis of sorted Contol (Con) or Hsf1KO MLL-AF9 LSCs (isolated from 2 full blown individual leukemia mice for each genotype). Hsf1 ablation (a) downregulated its known targets—heat shock protein genes; (b) upregulated genes related to myeloid differentiation (Itgam, Elane, Mpo) and downregulated stemness related genes (CD34, Flt3, Bcat1), and (c) genes related to OXPHOS. d–f GSEA revealed that Hsf1 deletion impaired stem cell signature (d), down-regulated genes related to OXPHOS (e) and TCA cycle (f). g CUT&RUN peak call enrichment analyses. KEGG and Gene ontology terms derived from genes involved in top 8000 peaks. h CUT&RUN demonstrated HSF1 binds Sdhc directly. H3K4me3 shows that HSF1 binding occurs in active chromatin region. Binding to genes encoding heat shock proteins (Hspd1 and Hspe1) and IgG binding were used as positive and negative controls, respectively.