STAT1 is required to maintain protective transcriptional programs in homeostatic HSCs including inhibition of cell cycling. (A) Diffusion map showing a proportion of STAT1-deficient HSCs occupy space distinct from WT HSCs. WT ESLAM, dark blue dots; STAT1KO ESLAM HSCs, light green dots. (B) Volcano plot of differentially expressed genes (red dots) using DESEq2 and Benjamini-Hochberg corrected P values at a significance level of .01. (C) Heatmap showing MHCI gene expression and hierarchical clustering of ESLAM HSCs from STAT1KO or WT mice. (D) STAT1-deficient HSCs expressed reduced levels of genes involved in virus life cycle, viral sensing, and genes in pathways that activate transcription of IFN and IFN-stimulated genes. Violin plots showing normalized expression. (E) Pathway enrichment analysis showing downregulated Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in STAT1-deficient ESLAM HSCs. Statistical significance is indicated by −Log₁₀(P.adj). (F) Gene set enrichment analysis (GSEA) plots showing significant enrichment of cell cycle related signatures in STAT1-deficient ESLAM HSCs. NES and FDR are indicated. FDR, false discovery rate; KO, knockout; NES, normalized enrichment score; P.adj., adjusted P value.