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DNA methylation in human gastric epithelial cells defines regional identity without restricting lineage plasticity.
Fritsche, Kristin; Boccellato, Francesco; Schlaermann, Philipp; Koeppel, Max; Denecke, Christian; Link, Alexander; Malfertheiner, Peter; Gut, Ivo; Meyer, Thomas F; Berger, Hilmar.
Afiliação
  • Fritsche K; Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117, Berlin, Germany.
  • Boccellato F; Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117, Berlin, Germany.
  • Schlaermann P; Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
  • Koeppel M; Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117, Berlin, Germany.
  • Denecke C; Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117, Berlin, Germany.
  • Link A; Center for Bariatric and Metabolic Surgery, Center of Innovative Surgery (ZIC), Department of Surgery, Campus Virchow Klinikum and Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • Malfertheiner P; Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-Von-Guericke University Hospital, Magdeburg, Germany.
  • Gut I; Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-Von-Guericke University Hospital, Magdeburg, Germany.
  • Meyer TF; Centro Nacional de Análisis Genómico (CNAG-CRG), Barcelona, Spain.
  • Berger H; Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117, Berlin, Germany. tfm@mpiib-berlin.mpg.de.
Clin Epigenetics ; 14(1): 193, 2022 12 30.
Article em En | MEDLINE | ID: mdl-36585699
BACKGROUND: Epigenetic modifications in mammalian DNA are commonly manifested by DNA methylation. In the stomach, altered DNA methylation patterns have been observed following chronic Helicobacter pylori infections and in gastric cancer. In the context of epigenetic regulation, the regional nature of the stomach has been rarely considered in detail. RESULTS: Here, we establish gastric mucosa derived primary cell cultures as a reliable source of native human epithelium. We describe the DNA methylation landscape across the phenotypically different regions of the healthy human stomach, i.e., antrum, corpus, fundus together with the corresponding transcriptomes. We show that stable regional DNA methylation differences translate to a limited extent into regulation of the transcriptomic phenotype, indicating a largely permissive epigenetic regulation. We identify a small number of transcription factors with novel region-specific activity and likely epigenetic impact in the stomach, including GATA4, IRX5, IRX2, PDX1 and CDX2. Detailed analysis of the Wnt pathway reveals differential regulation along the craniocaudal axis, which involves non-canonical Wnt signaling in determining cell fate in the proximal stomach. By extending our analysis to pre-neoplastic lesions and gastric cancers, we conclude that epigenetic dysregulation characterizes intestinal metaplasia as a founding basis for functional changes in gastric cancer. We present insights into the dynamics of DNA methylation across anatomical regions of the healthy stomach and patterns of its change in disease. Finally, our study provides a well-defined resource of regional stomach transcription and epigenetics.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Helicobacter pylori / Infecções por Helicobacter Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Helicobacter pylori / Infecções por Helicobacter Idioma: En Ano de publicação: 2022 Tipo de documento: Article