Regulon analysis implicated several unexpected TFs in regulating the transcriptome of SSc fibroblast differentiation, particularly STAT1, FOSL2, RUNX1, IRF7, HIF1A, CREB3L1, and FOXP1, as well as SMAD3. IRF7 is upstream69 and STAT1 downstream70,71 interferon signaling, previously implicated in SSc skin41. This evidence concerns the gene FOSL2 and systemic sclerosis.