1. Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium
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Béatrice Romagnolo, François Gerbe, Leila Makrini, Noah F. Shroyer, Johan H. van Es, Christine Pignodel, Sylvie Robine, Georg Mellitzer, Philippe Jay, Bénédicte Brulin, Hans Clevers, Jean-François Bourgaux, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Division of Gastroenterology, Hepatology and Nutrition, University of Cincinnati (UC)-Cincinnati Children's Hospital Medical Center, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service d'Anatomopathologie, Hubrecht Institute for Developmental Biology and Stem Cell Research, Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS)
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Adenoma ,Cell type ,Cellular differentiation ,Nerve Tissue Proteins ,Enteroendocrine cell ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,SOX9 ,Adenocarcinoma ,Protein Serine-Threonine Kinases ,Biology ,Article ,Mice ,03 medical and health sciences ,Doublecortin-Like Kinases ,0302 clinical medicine ,Intestinal mucosa ,Intestinal Neoplasms ,Intestine, Small ,Basic Helix-Loop-Helix Transcription Factors ,Animals ,Humans ,Intestine, Large ,Intestinal Mucosa ,Isomerases ,Research Articles ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,Membrane Proteins ,Cell Differentiation ,SOX9 Transcription Factor ,Cell Biology ,Intestinal epithelium ,Cell biology ,Intramolecular Oxidoreductases ,Mice, Inbred C57BL ,Cyclooxygenase 2 ,030220 oncology & carcinogenesis ,Cyclooxygenase 1 ,Tuft cell ,Stem cell ,Biomarkers - Abstract
Tuft cells represent a fourth type of intestinal secretory cell that constitutes the primary source of endogenous intestinal opioids and are the only epithelial cell that constitutively express cyclooxygenases., The unique morphology of tuft cells was first revealed by electron microscopy analyses in several endoderm-derived epithelia. Here, we explore the relationship of these cells with the other cell types of the intestinal epithelium and describe the first marker signature allowing their unambiguous identification. We demonstrate that although mature tuft cells express DCLK1, a putative marker of quiescent stem cells, they are post-mitotic, short lived, derive from Lgr5-expressing epithelial stem cells, and are found in mouse and human tumors. We show that whereas the ATOH1/MATH1 transcription factor is essential for their differentiation, Neurog3, SOX9, GFI1, and SPDEF are dispensable, which distinguishes these cells from enteroendocrine, Paneth, and goblet cells, and raises from three to four the number of secretory cell types in the intestinal epithelium. Moreover, we show that tuft cells are the main source of endogenous intestinal opioids and are the only epithelial cells that express cyclooxygenase enzymes, suggesting important roles for these cells in the intestinal epithelium physiopathology.
- Published
- 2011
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