ArticleNature genetics2022
Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemo-resistant pancreatic cancer.
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Article in Nature genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers.
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172citing papers in PubMed
28.0field-weighted citation impact, top 1% of its field
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Who cites it
172 citing papers in PubMed, 270 citations in OpenAlex.
- Integrative single-cell and spatial transcriptomic approaches to decipher the tumor microenvironment and therapeutic resistance in pancreatic cancer.Cancer biology & therapy · 2026Review
- Clonal heterogeneity in human pancreatic ductal adenocarcinoma and its impact on tumor progression.Nature genetics · 2026Article
- Cell plasticity in cancer and therapy resistance.Experimental & molecular medicine · 2026Review
- Periductal Fibroblast Density Defines Lymphocyte Exclusion via a CD44-Dependent Stromal Checkpoint in Pancreatic Cancer.Cancer immunology research · 2026Article
- IFNγ-dependent tumor-cell MHC-II is restrained by MAPK signaling and associated with immunotherapy responsiveness in pancreatic ductal adenocarcinoma.Cancer immunology research · 2026Article
- Uncovering pan-cancer signatures of chemoresistance.Genome medicine · 2026Article
- Article
- Exploratory single-nucleus multiomics analysis of myeloid cell states associated with neoadjuvant chemotherapy response in pancreatic ductal adenocarcinoma.Clinical and translational medicine · 2026Article
- Spatial Mapping of the Precancer-to-Cancer Transition in Breast and Prostate.Cancer discovery · 2026Article
- A Generalizable and Interpretable Framework for Molecular Subtype Classification of Pancreatic Ductal Adenocarcinoma Integrating Conformal Uncertainty Quantification and Consensus-Based Explainable Artificial Intelligence Across Multiple Cohorts.International journal of molecular sciences · 2026Article
- GDF15 promotes 5-Fluorouracil and Oxaliplatin resistance by promoting stem cell-like phenotype in colorectal cancer.British journal of cancer · 2026Article
- Advances in deciphering intratumoral versus peritumoral heterogeneity of infiltrating lymphocytes in pancreatic cancer: a spatial perspective.Translational oncology · 2026Review
- Spatially resolved tissue architecture and computational pathology in pancreatic cancer.Experimental & molecular medicine · 2026Review
- ViMST: vision transformer-based dual modality multi-task graph contrastive network for spatial transcriptomics microenvironments investigation.BMC biology · 2026Article
- Malignant epithelial states drive immune dysfunction in ampulla of Vater carcinoma.Biomarker research · 2026Article
- IL1RAP-expressing myeloid-stromal networks represent a therapeutic vulnerability to improve chemoimmunotherapy sensitivity in pancreatic cancer.JCI insight · 2026Article
- Hierarchical classification of immune cell transcriptomes at population-scale.bioRxiv : the preprint server for biology · 2026Article
- Agrimol B inhibits pancreatic ductal adenocarcinoma by induction of lethal mitophagy through decreasing mitochondrial transcription termination factor 3.Precision clinical medicine · 2026Article
- GLIS3 marks a neural-like progenitor cell state that drives metastasis in pancreatic ductal adenocarcinoma.Cell reports · 2026Article
- Pan-cancer analysis of spatial transcriptomics reveals heterogeneous tumor spatial microenvironment.Cell reports. Medicine · 2026Article
112 more citing papers are in PubMed but not listed here.
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Authors and funding
66 authors at 5 institutions in 1 country.
Daniel Cui Zhou *Department of Medicine, Washington University in St Louis, St Louis, MO, USA.ORCID http://orcid.org/0000-0002-7834-2778
Reyka G Jayasinghe *Department of Medicine, Washington University in St Louis, St Louis, MO, USA.
Siqi ChenDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
John M HerndonDepartment of Surgery, Washington University in St Louis, St Louis, MO, USA.ORCID http://orcid.org/0000-0002-8378-9654
Michael D IglesiaDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.ORCID http://orcid.org/0000-0002-0841-2144
Pooja NavaleDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Michael C WendlMcDonnell Genome Institute, Washington University in St Louis, St Louis, MO, USA.
Wagma CaravanDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.ORCID http://orcid.org/0000-0003-4082-6723
Kazuhito SatoDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.ORCID http://orcid.org/0000-0003-0589-7454
Erik StorrsDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Chia-Kuei MoDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Jingxian LiuDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.ORCID http://orcid.org/0000-0002-2172-3297
Austin N Southard-SmithDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Yige WuDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Nataly Naser Al DeenDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
John M BaerDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Robert S FultonMcDonnell Genome Institute, Washington University in St Louis, St Louis, MO, USA.
Matthew A WyczalkowskiDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.ORCID http://orcid.org/0000-0003-4197-551X
Ruiyang LiuDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Catrina C FronickMcDonnell Genome Institute, Washington University in St Louis, St Louis, MO, USA.
Lucinda A FultonMcDonnell Genome Institute, Washington University in St Louis, St Louis, MO, USA.
Andrew ShinkleDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Lisa ThammavongDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Houxiang ZhuDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Hua SunDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.ORCID http://orcid.org/0000-0003-2169-0808
Liang-Bo WangDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.ORCID http://orcid.org/0000-0001-6977-9348
Yize LiDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.ORCID http://orcid.org/0000-0003-1074-281X
Chong ZuoDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Joshua F McMichaelDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.ORCID http://orcid.org/0000-0002-0197-2245
Sherri R DaviesDepartment of Surgery, Washington University in St Louis, St Louis, MO, USA.ORCID http://orcid.org/0000-0002-7141-8354
Elizabeth L AppelbaumMcDonnell Genome Institute, Washington University in St Louis, St Louis, MO, USA.
Keenan J RobbinsDepartment of Surgery, Washington University in St Louis, St Louis, MO, USA.ORCID http://orcid.org/0000-0001-6950-175X
Sara E ChasnoffDepartment of Surgery, Washington University in St Louis, St Louis, MO, USA.
Xiaolu YangDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Ashley N ReebDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Clara OhDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Mamatha SerasanambatiDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Preet LalDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Rajees VargheseDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Jay R MashlDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Jennifer PonceMcDonnell Genome Institute, Washington University in St Louis, St Louis, MO, USA.
Nadezhda V TerekhanovaDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Lijun YaoDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Fang WangDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lijun ChenDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Michael SchnaubeltDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rita Jui-Hsien LuDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.ORCID http://orcid.org/0000-0002-7434-6544
Julie K SchwarzSiteman Cancer Center, Washington University in St Louis, St Louis, MO, USA.
Sidharth V PuramDepartment of Otolaryngology-Head & Neck Surgery, Washington University in St Louis, St Louis, MO, USA.
Albert H KimSiteman Cancer Center, Washington University in St Louis, St Louis, MO, USA.ORCID http://orcid.org/0000-0002-1751-8493
Sheng-Kwei SongDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Kooresh I ShoghiDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Ken S LauDepartment of Cell and Developmental Biology and Epithelial Biology Center, Vanderbilt University School of Medicine, Vanderbilt, TN, USA.ORCID http://orcid.org/0000-0001-8438-0319
Tao JuDepartment of Computer Science and Engineering, Washington University in St Louis, St Louis, MO, USA.
Ken ChenDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-4013-5279
Deyali ChatterjeeDepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
William G HawkinsDepartment of Surgery, Washington University in St Louis, St Louis, MO, USA.ORCID http://orcid.org/0000-0001-7087-3585
Hui ZhangDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Samuel AchilefuDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Milan G ChhedaDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
Stephen T OhDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
William E GillandersDepartment of Surgery, Washington University in St Louis, St Louis, MO, USA.
Feng ChenDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA.
David G DeNardoDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA. ddenardo@wustl.edu.ORCID http://orcid.org/0000-0002-3655-5783
Ryan C FieldsDepartment of Surgery, Washington University in St Louis, St Louis, MO, USA. rcfields@wustl.edu.ORCID http://orcid.org/0000-0001-6176-8943
Li DingDepartment of Medicine, Washington University in St Louis, St Louis, MO, USA. lding@wustl.edu.ORCID http://orcid.org/0000-0003-1517-2975
James S. McDonnell Foundation · USWashington University in St. Louis · USJohns Hopkins University · USThe University of Texas MD Anderson Cancer Center · USVanderbilt University · US
Funding
Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0MSURGICAL ONCOLOGY TRAINING GRANTT32CA009621 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN, William E. Gillanders · 1988 to 2026
$12.9MWASHINGTON UNIVERSITY HUMAN TUMOR ATLAS RESEARCH CENTERU2CCA233303 · NCI · WASHINGTON UNIVERSITY · PI DING, LI · 2018 to 2023
$9.7MWASHINGTON UNIVERSITY CO-CLINICAL IMAGING RESEARCH RESOURCEU24CA209837 · NCI · WASHINGTON UNIVERSITY · PI Li Ding, Shunqiang Li · 2017 to 2026
$6.3MNANOPHOTOSENSITIZERS FOR REGENERATIVE PHOTOTHERAPYR01CA260855 · NCI · WASHINGTON UNIVERSITY · PI ACHILEFU, SAMUEL · 2021 to 2025
$3.5MPathogenic Variant Discovery Across a Broad Spectrum of Human DiseasesR01HG009711 · NHGRI · WASHINGTON UNIVERSITY · PI CHEN, FENG, DING, LI · 2017 to 2020
$2.2MDeep Discovery and Clinical Interpretation of Germline and Somatic Cancer DriversU24CA211006 · NCI · WASHINGTON UNIVERSITY · PI DING, LI, GOVINDAN, RAMASWAMY · 2016 to 2020
$1.8MNCI NIH HHS P30 CA091842NCI NIH HHS R01 CA260855NCI NIH HHS T32 CA009621NCI NIH HHS U24 CA209837NCI NIH HHS U24 CA211006NCI NIH HHS U2C CA233303NHGRI NIH HHS R01 HG009711
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.
Indexed as
Carcinoma, Pancreatic DuctalPancreatic NeoplasmsCell Transformation, NeoplasticHumansPancreasTumor Microenvironment
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