Fig. 3

iCAFs and myCAFs reside in the interlobular and lobular steady states, respectively. a Micrographs of immunoperoxidase-stained cultures from CAF1 and normal-derived fibroblasts showing coordinated expression of PDGFRβ and tenascin within interlobular fibroblasts and iCAFs as well as within lobular fibroblasts and myCAFs independently of state. By comparison, the interlobular lineage marker, CD26, is state-dependent. Nuclei counterstained by hematoxylin. Scale bar = 50 μm. b Gene set enrichment analysis (GSEA) plots depicting significant enrichment between iCAFs and an interlobular gene set (upper) and a significant enrichment between myCAFs and a lobular gene set (lower). ES: Enrichment Score. NES: Normalized Enrichment Score. FDR: false discovery rate. c A heatmap representing a CAF signature of 31 literature curated CAF markers in iCAFs, myCAFs, interlobular and lobular fibroblasts. The red bar indicates the 26 CAF subtype-specific markers differentially expressed between iCAFs and myCAFs (≥ 5 FPKM, ≥ 2-fold change, adjusted p < 0.01). The green bar indicates the 15 CAF-specific markers elevated in either CAF type compared to both steady-state fibroblasts (≥ 5 FPKM, ≥ 2-fold change, adjusted p < 0.01). Note that most CAF markers exhibit CAF subtype-specific expression and that none of the CAF markers are elevated in the normal-derived interlobular or lobular fibroblasts compared to both perturbed states. The CAF signature is based on [26, 28, 29]. Key indicates row-z-score