{"id":"doi:10.1038/s41588-022-01157-1","kind":"article","title":"Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemo-resistant pancreatic cancer","authors":["Cui Zhou D","Jayasinghe RG","Chen S","Herndon JM","Iglesia MD","Navale P","Wendl MC","Caravan W","Sato K","Storrs E","Mo CK","Liu J","Southard-Smith AN","Wu Y","Naser Al Deen N","Baer JM","Fulton RS","Wyczalkowski MA","Liu R","Fronick CC","Fulton LA","Shinkle A","Thammavong L","Zhu H","Sun H"],"author_count":66,"year":2022,"published":"2022-08-22","venue":"Nature genetics","cited_by":262,"doi":"10.1038/s41588-022-01157-1","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41588-022-01157-1","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41588-022-01157-1","updated":null,"pmid":"35995947","pmcid":"PMC9470535","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC9470535/pdf","abstract":"Pancreatic ductal adenocarcinoma is a lethal disease with limited treatment options and poor survival. We studied 83 spatial samples from 31 patients (11 treatment-naïve and 20 treated) using single-cell/nucleus RNA sequencing, bulk-proteogenomics, spatial transcriptomics and cellular imaging. Subpopulations of tumor cells exhibited signatures of proliferation, KRAS signaling, cell stress and epithelial-to-mesenchymal transition. Mapping mutations and copy number events distinguished tumor populations from normal and transitional cells, including acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia. Pathology-assisted deconvolution of spatial transcriptomic data identified tumor and transitional subpopulations with distinct histological features. We showed coordinated expression of TIGIT in exhausted and regulatory T cells and Nectin in tumor cells. Chemo-resistant samples contain a threefold enrichment of inflammatory cancer-associated fibroblasts that upregulate metallothioneins. Our study reveals a deeper understanding of the intricate substructure of pancreatic ductal adenocarcinoma tumors that could help improve therapy for patients with this disease.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemo-resistant pancreatic cancer\" by Cui Zhou D, Jayasinghe RG, Chen S et al., https://doi.org/10.1038/s41588-022-01157-1, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"single-cell-spatial","name":"Single-Cell & Spatial Omics","domain_slug":"biotech"}],"cited_in_dossiers":[]}