{
  "abstract": "Background A resemblance of pancreatic tumours to their native tissue architecture remains largely unexplored, while it may reveal novel insights into healthy and diseased tissue.Objective This study aims at generating a spatially resolved map of human pancreatic duct cell populations in the native tissue and in tumours, that is, pancreatic ductal adenocarcinoma (PDAC) and adenosquamous carcinoma of the pancreas (ASCP).Design New datasets were acquired with several spatial transcriptomics platforms integrated with public single-cell RNAseq datasets and validated by multiplex immunofluorescence. Cell lines and primary human cell cultures were genetically manipulated.Results Groups of Keratin-5 + cells in larger ducts have a gene signature reminiscent of stem cells and (supra)basal cells from other tissues. At single cell resolution, this group comprises ∆Np63+ basal cells (BAS) and ∆Np63− supra-basally residing luminal-B cells (LUM-B). The latter express previously unreported MUC4 and MUC16 and are distinct from other luminal cells in the ducts. In cancer, BAS and LUM-B signatures associate with basal-like (BL) PDAC and correlate with lower survival. However, PDAC exhibits a random spatial pattern and fragmented native expression programmes while ASCP preserves the identity of LUM-B and BAS in a spatially unmixed pattern. ∆Np63 drives cell plasticity to BAS, conserved from the native tissue to cancer.Conclusion Spatially distinct duct cell populations are revealed, and the extent of preservation of the native cell identities in pancreatic cancer underpins distinct tumour identities. This warrants separate consideration in research and therapy.",
  "authors": [
    {
      "affiliations": [
        "Translational Oncology Research Centre - Laboratory for Medical and Molecular Oncology, Vrije Universiteit Brussel, Brussels, Belgium",
        "BruPaCT, Brussels, Belgium"
      ],
      "name": "Jan-Lars Van den Bossche"
    },
    {
      "affiliations": [
        "Translational Oncology Research Centre - Laboratory for Medical and Molecular Oncology, Vrije Universiteit Brussel, Brussels, Belgium",
        "BruPaCT, Brussels, Belgium"
      ],
      "name": "Melissa Van der Vliet"
    },
    {
      "affiliations": [
        "Translational Oncology Research Centre - Laboratory for Medical and Molecular Oncology, Vrije Universiteit Brussel, Brussels, Belgium",
        "BruPaCT, Brussels, Belgium"
      ],
      "name": "Ellis Michiels"
    },
    {
      "affiliations": [
        "BruPaCT, Brussels, Belgium",
        "Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium"
      ],
      "name": "Oier Azurmendi Senar"
    },
    {
      "affiliations": [
        "Translational Oncology Research Centre - Laboratory for Medical and Molecular Oncology, Vrije Universiteit Brussel, Brussels, Belgium",
        "BruPaCT, Brussels, Belgium"
      ],
      "name": "Silke Van Lint"
    },
    {
      "affiliations": [
        "Translational Oncology Research Centre - Laboratory for Medical and Molecular Oncology, Vrije Universiteit Brussel, Brussels, Belgium"
      ],
      "name": "Zeynep Madran"
    },
    {
      "affiliations": [
        "Translational Oncology Research Centre - Laboratory for Medical and Molecular Oncology, Vrije Universiteit Brussel, Brussels, Belgium",
        "BruPaCT, Brussels, Belgium"
      ],
      "name": "Katarina Coolens"
    },
    {
      "affiliations": [
        "Translational Oncology Research Center, Vrije Universiteit Brussel, Brussels, Belgium"
      ],
      "name": "Jack Brons"
    },
    {
      "affiliations": [
        "CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Bellvitge Biomedical Research Institute (IDIBELL), Bellvitge University Hospital, Barcelona, Spain"
      ],
      "name": "Montserrat Nacher"
    },
    {
      "affiliations": [
        "BruPaCT, Brussels, Belgium",
        "Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium"
      ],
      "name": "Tatjana Arsenijevic"
    },
    {
      "affiliations": [
        "BruPaCT, Brussels, Belgium",
        "Department of Hepatopancreatobiliary Surgery, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Europe Hospitals, Brussels, Belgium"
      ],
      "name": "Nouredin Messaoudi"
    },
    {
      "affiliations": [
        "Department of Pathology, Universitair Ziekenhuis Brussel, Brussels, Belgium"
      ],
      "name": "Pierre Lefesvre"
    },
    {
      "affiliations": [
        "BruPaCT, Brussels, Belgium",
        "Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium"
      ],
      "name": "Christelle Bouchart"
    },
    {
      "affiliations": [
        "BruPaCT, Brussels, Belgium",
        "Centre d'Anatomie Pathologique, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium"
      ],
      "name": "Laurine Verset"
    },
    {
      "affiliations": [
        "Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium",
        "Department of Digestive Surgery, Unit of Hepatobiliary Surgery and Transplantation, Hôpitaux Universitaires de Bruxelles (HUB), Hôpital Erasme, Brussels, Belgium"
      ],
      "name": "Julie Navez"
    },
    {
      "affiliations": [
        "Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium",
        "Centre d'Anatomie Pathologique, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium"
      ],
      "name": "Jennifer Fallas"
    },
    {
      "affiliations": [
        "Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Marseille, France"
      ],
      "name": "Nelson Dusetti"
    },
    {
      "affiliations": [
        "CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Bellvitge Biomedical Research Institute (IDIBELL), Bellvitge University Hospital, Barcelona, Spain",
        "Department of Clinical Sciences, University of Barcelona, Barcelona, Spain"
      ],
      "name": "Eduard Montanya"
    },
    {
      "affiliations": [
        "Pancreas Regeneration Group, Oncobell, IDIBELL, Barcelona, Spain",
        "Department of Physiological Science, School of Medicine, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain"
      ],
      "name": "Meritxell Rovira"
    },
    {
      "affiliations": [
        "Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium",
        "Department of Gastroenterology, Université Libre de Bruxelles, HUB Bordet Erasme Hospital, Brussels, Belgium"
      ],
      "name": "Jean-Luc Van Laethem"
    },
    {
      "affiliations": [
        "Translational Oncology Research Centre - Laboratory for Medical and Molecular Oncology, Vrije Universiteit Brussel, Brussels, Belgium",
        "BruPaCT, Brussels, Belgium"
      ],
      "name": "Isabelle Houbracken"
    },
    {
      "affiliations": [
        "Translational Oncology Research Centre - Laboratory for Medical and Molecular Oncology, Vrije Universiteit Brussel, Brussels, Belgium",
        "BruPaCT, Brussels, Belgium"
      ],
      "name": "Jonathan Baldan"
    },
    {
      "affiliations": [
        "Translational Oncology Research Centre - Laboratory for Medical and Molecular Oncology, Vrije Universiteit Brussel, Brussels, Belgium",
        "BruPaCT, Brussels, Belgium"
      ],
      "name": "Ilse Rooman"
    }
  ],
  "title": "Luminal–basal stratification of the native human pancreatic duct is differentially represented in pancreatic cancers",
  "uid": "5b77ef80-c14d-509d-8a0e-654eeec18822"
}