We next inferred from pseudotime analysis the various genes driving tumor cell progression trajectory (Supplementary Data 6) and overlapped the identified genes with a series of known secreted CAF activators (transforming growth factor-β (TGF-β), other TGF-β superfamily members, platelet-derived growth factors (PDGFs), epidermal growth factor (EGF) family members, fibroblast growth factors (FGFs) and sonic hedgehog (SHH))38 (Fig. 6a). This evidence concerns the gene SHH and neoplasm.