Integrative analysis reveals AZA-sensitive genes crucial to stromal HSPC support. (A) Gene set enrichment analysis of our RNA-seq data showing significant upregulation of stromal HSPC-supportive genes (published reference gene set¹³ ) in AZA-treated EL08-1D2 cells. (B) We identified 4 distinct gene coexpression modules where each module was given an arbitrary color (blue, IFN-signaling pathway; brown, ECM receptor interaction; and turquoise, WNT- and PDGF-signaling pathways). Both the blue and the brown modules significantly correlated with AZA treatment (Pearson correlation, P = 2.1e-09 [blue] and 3.4e-08 [brown], respectively) and contained significantly more genes that were significantly regulated by AZA compared with untreated controls (Fisher's exact test, P = 4.22e-10 [blue] and 0.0184 [brown]). ***P < .001. (C) Detailed network of the ECM receptor interaction (brown) module showing significantly enriched biological pathways and their genes. Colors indicate log2-fold change in gene expression in AZA-treated samples vs untreated controls. Hub genes are shown in bold letters. (D) Venn diagram of meta-analysis showing overlap of 21 genes (in red) between AZA-sensitive downregulated EL08-1D2 genes (green) and upregulated genes in MDS MSCs in comparison with healthy controls (blue). The 7 identified collagen genes are listed at the bottom of the panel. NES, normalized enrichment score.