Spatial mapping of transcriptomic and lineage plasticity in metastatic pancreatic cancer

Patients with treatment-refractory pancreatic cancer often succumb to widespread systemic metastases; however, the transcriptomic heterogeneity that underlies recalcitrance to therapy remains understudied, particularly in the spatial context. We constructed high-resolution spatial maps of transcriptional heterogeneity, clonal architecture and lineage plasticity using spatially resolved transcriptomics from 55 individual samples of primary tumour, liver, lung, and peritoneal metastases, collected from 13 patients via a rapid ("warm") autopsy program. Additionally, we validated the lineage composition and spatial distribution using patient-derived xenograft (PDX) models generated from the primary tumours of two patients. Visium spatial transcriptomics (10X Genomics) was performed on fresh frozen or FFPE tissues. To minimize batch effects, primary and their matched metastatic samples from the same patients were loaded onto the same Visium slide.