Bulk RNA-seq of WNT-responsive and WNT-secreting cancer cell populations from orthotopic PDAC tumors

Pancreatic ductal adenocarcinoma (PDAC) exhibits pronounced intratumoral heterogeneity driven in part by WNT signaling dynamics. To characterize transcriptional differences among distinct WNT signaling states in vivo, we performed bulk RNA sequencing of fluorescence-activated cell sorting (FACS)-isolated cancer cell populations from orthotopic PDAC tumors. WNT-responsive (WNT-R), WNT-secreting (WNT-S), double-positive (WNT-R/S), and double-negative (DN) cancer cells were isolated from KPC 7TCF-eGFP/Porcn-DMA reporter tumors. RNA libraries were prepared using the SMARTerSeq2 protocol and sequenced from four biological replicates per group. Differential gene expression analysis revealed enrichment of canonical WNT/β-catenin target genes in WNT-R cells, elevated Porcn expression in WNT-S cells, and intermediate transcriptional profiles in WNT-R/S cells, validating the fidelity of the reporter system in vivo. This dataset provides a resource for dissecting WNT-dependent cancer cell states and signaling interactions in PDAC.