TY - JOUR T1 - Discovery and 3D imaging of a novel ΔNp63-expressing basal cell type in human pancreatic ducts with implications in disease JF - Gut JO - Gut SP - 2030 LP - 2042 DO - 10.1136/gutjnl-2020-322874 VL - 71 IS - 10 AU - Sandrina Martens AU - Katarina Coolens AU - Mathias Van Bulck AU - Tatjana Arsenijevic AU - Joan Casamitjana AU - Angel Fernandez Ruiz AU - Abdessamad El Kaoutari AU - Jaime Martinez de Villareal AU - Hediel Madhloum AU - Farzad Esni AU - Yves Heremans AU - Gunter Leuckx AU - Harry Heimberg AU - Luc Bouwens AU - Patrick Jacquemin AU - Diedert Luc De Paep AU - Peter in't Veld AU - Nicky D'Haene AU - Christelle Bouchart AU - Nelson Dusetti AU - Jean-Luc Van Laethem AU - Wim Waelput AU - Pierre Lefesvre AU - Francisco X Real AU - Meritxell Rovira AU - Ilse Rooman Y1 - 2022/10/01 UR - http://gut.bmj.com/content/71/10/2030.abstract N2 - Objective The aggressive basal-like molecular subtype of pancreatic ductal adenocarcinoma (PDAC) harbours a ΔNp63 (p40) gene expression signature reminiscent of a basal cell type. Distinct from other epithelia with basal tumours, ΔNp63+ basal cells reportedly do not exist in the normal pancreas.Design We evaluated ΔNp63 expression in human pancreas, chronic pancreatitis (CP) and PDAC. We further studied in depth the non-cancerous tissue and developed a three-dimensional (3D) imaging protocol (FLIP-IT, Fluorescence Light sheet microscopic Imaging of Paraffin-embedded or Intact Tissue) to study formalin-fixed paraffin-embedded samples at single cell resolution. Pertinent mouse models and HPDE cells were analysed.Results In normal human pancreas, rare ΔNp63+ cells exist in ducts while their prevalence increases in CP and in a subset of PDAC. In non-cancer tissue, ΔNp63+ cells are atypical KRT19+ duct cells that overall lack SOX9 expression while they do express canonical basal markers and pertain to a niche of cells expressing gastrointestinal stem cell markers. 3D views show that the basal cells anchor on the basal membrane of normal medium to large ducts while in CP they exist in multilayer dome-like structures. In mice, ΔNp63 is not found in adult pancreas nor in selected models of CP or PDAC, but it is induced in organoids from larger Sox9low ducts. In HPDE, ΔNp63 supports a basal cell phenotype at the expense of a classical duct cell differentiation programme.Conclusion In larger human pancreatic ducts, basal cells exist. ΔNp63 suppresses duct cell identity. These cells may play an important role in pancreatic disease, including PDAC ontogeny, but are not present in mouse models.Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. All relevant data can be requested by contacting the corresponding author. ER -