Hypoxia potentiates the inflammatory fibroblast phenotype promoted by pancreatic cancer cell-derived cytokines

Cancer-associated fibroblasts (CAFs) are a major cell type in the stroma of solid tumors and can exert both tumor-promoting and tumor-restraining functions. This functional heterogeneity is correlated with the existence of transcriptionally distinct subpopulations of CAFs. While CAF heterogeneity can be driven in part by tumor cell-produced cytokines, other determinants shaping CAF identity and function are largely unknown. Here, we investigated the role of hypoxia in regulating CAF heterogeneity in PDAC Overall design: RNA-sequencing of PSC cells expressing a control sgRNA (R26-sg1) or HIF-1a targeting sgRNA (HIF1a-sg2), cultured in normoxia (20% O2) or hypoxia (0.5% O2) for 48h