Transfer learning reveals cancer-associated fibroblasts are associated with epithelial-mesenchymal transition and inflammation in cancer cells in pancreatic ductal adenocarcinoma release_mnqfj5ov4fgetgihofy7cdwv5u

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment enriched with cancer associated fibroblasts (CAFs). This study utilized a convergence approach to identify tumor cell and CAF interactions through the integration of single-cell data from human tumors with human organoid co-culture experiments. Analysis of a comprehensive atlas of PDAC single-cell RNA sequencing (scRNA-seq) data indicated that CAF density is associated with increased inflammation and epithelial-mesenchymal transition (EMT) in epithelial cells. Transfer learning using transcriptional data from patient-derived organoid and CAF co-cultures provided in silico validation of CAF induction of inflammatory and EMT epithelial cell states. Further experimental validation in co-cultures demonstrated integrin beta 1 (ITGB1) and vascular endothelial factor A (VEGF-A) interactions with neuropilin-1 (NRP1) mediating CAF-epithelial cell crosstalk. Together, this study introduces transfer learning from human single-cell data to organoid co-culture analyses for experimental validation of discoveries of cell-cell crosstalk and identifies fibroblast-mediated regulation of EMT and inflammation.
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