Fig. 4: Reprogramming of differentiated macrophages by selected compounds.

a Number of DEGs induced by each compound. Orange: upregulated genes. Blue: downregulated genes. Compounds labeled in purple are FDA-approved drugs. hMDMs were differentiated into either M2 by IL-4 plus IL-13 or M1 by IFNγ plus TNFα and duplicate samples were then treated with either M1-activating or M2-activating compounds, respectively, at the effective concentrations. Controls include two differentiated M1 and M2 macrophages, M2 macrophages treated with IFNγ and M1 macrophages treated with IL-4. Gene expression in each sample was measured by RNA-seq separately. b Hierarchical clustering heatmap of Pearson correlation coefficients for 7620 DEGs induced by compounds as well as IFNγ and IL-4. c GSEA analysis of transcriptional responses to each compound as compared to IFNγ and IL-4. The numerical numbers on the right indicate module numbers identified by Xu et al.6. d Network of GO enriched terms using BiNGO on top 10% central hubs genes (n = 1255) of macrophage activation network. Node color and size represent the FDR values of enriched GO terms. New pathways identified in this study are labeled in red. e, f Functional enrichment analysis of DEGs induced by each compound. Shared (e) and unique pathways (f) are shown. Compound targets and FDA-approval information are indicated. The order of M1-activating and M2-activarting compounds in e and f are the same as in a.