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PanIN and CAF transitions in pancreatic carcinogenesis revealed with spatial data integration.
Bell, Alexander T F; Mitchell, Jacob T; Kiemen, Ashley L; Lyman, Melissa; Fujikura, Kohei; Lee, Jae W; Coyne, Erin; Shin, Sarah M; Nagaraj, Sushma; Deshpande, Atul; Wu, Pei-Hsun; Sidiropoulos, Dimitrios N; Erbe, Rossin; Stern, Jacob; Chan, Rena; Williams, Stephen; Chell, James M; Ciotti, Lauren; Zimmerman, Jacquelyn W; Wirtz, Denis; Ho, Won Jin; Zaidi, Neeha; Thompson, Elizabeth; Jaffee, Elizabeth M; Wood, Laura D; Fertig, Elana J; Kagohara, Luciane T.
Affiliation
  • Bell ATF; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Mitchell JT; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medici
  • Kiemen AL; Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Lyman M; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Fujikura K; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Lee JW; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medici
  • Coyne E; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medici
  • Shin SM; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medici
  • Nagaraj S; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Deshpande A; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medici
  • Wu PH; Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
  • Sidiropoulos DN; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medici
  • Erbe R; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medici
  • Stern J; 10x Genomics, Pleasanton, CA, USA.
  • Chan R; 10x Genomics, Pleasanton, CA, USA.
  • Williams S; 10x Genomics, Pleasanton, CA, USA.
  • Chell JM; 10x Genomics, Pleasanton, CA, USA.
  • Ciotti L; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Zimmerman JW; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medici
  • Wirtz D; Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA; Department of Materials Science and Engineering, The Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, MD, US
  • Ho WJ; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medici
  • Zaidi N; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medici
  • Thompson E; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA; The Skip Viragh Center for Clinical and Translational Research, Baltimore, MD, USA.
  • Jaffee EM; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medici
  • Wood LD; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA; The Skip Viragh Center for Clinical and Translational Research, Baltimore, MD, USA.
  • Fertig EJ; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medici
  • Kagohara LT; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medici
Cell Syst ; 15(8): 753-769.e5, 2024 Aug 21.
Article in En | MEDLINE | ID: mdl-39116880
ABSTRACT
This study introduces a new imaging, spatial transcriptomics (ST), and single-cell RNA-sequencing integration pipeline to characterize neoplastic cell state transitions during tumorigenesis. We applied a semi-supervised analysis pipeline to examine premalignant pancreatic intraepithelial neoplasias (PanINs) that can develop into pancreatic ductal adenocarcinoma (PDAC). Their strict diagnosis on formalin-fixed and paraffin-embedded (FFPE) samples limited the single-cell characterization of human PanINs within their microenvironment. We leverage whole transcriptome FFPE ST to enable the study of a rare cohort of matched low-grade (LG) and high-grade (HG) PanIN lesions to track progression and map cellular phenotypes relative to single-cell PDAC datasets. We demonstrate that cancer-associated fibroblasts (CAFs), including antigen-presenting CAFs, are located close to PanINs. We further observed a transition from CAF-related inflammatory signaling to cellular proliferation during PanIN progression. We validate these findings with single-cell high-dimensional imaging proteomics and transcriptomics technologies. Altogether, our semi-supervised learning framework for spatial multi-omics has broad applicability across cancer types to decipher the spatiotemporal dynamics of carcinogenesis.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pancreatic Neoplasms / Carcinoma, Pancreatic Ductal / Carcinogenesis / Cancer-Associated Fibroblasts Limits: Humans Language: En Journal: Cell Syst Year: 2024 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pancreatic Neoplasms / Carcinoma, Pancreatic Ductal / Carcinogenesis / Cancer-Associated Fibroblasts Limits: Humans Language: En Journal: Cell Syst Year: 2024 Type: Article Affiliation country: United States