TY - JOUR A1 - Wallaschek, Nina A1 - Reuter, Saskia A1 - Silkenat, Sabrina A1 - Wolf, Katharina A1 - Niklas, Carolin A1 - Özge, Kayisoglu A1 - Aguilar, Carmen A1 - Wiegering, Armin A1 - Germer, Christoph-Thomas A1 - Kircher, Stefan A1 - Rosenwald, Andreas A1 - Shannon-Lowe, Claire A1 - Bartfeld, Sina T1 - Ephrin receptor A2, the epithelial receptor for Epstein-Barr virus entry, is not available for efficient infection in human gastric organoids JF - PLoS Pathogens N2 - Epstein-Barr virus (EBV) is best known for infection of B cells, in which it usually establishes an asymptomatic lifelong infection, but is also associated with the development of multiple B cell lymphomas. EBV also infects epithelial cells and is associated with all cases of undifferentiated nasopharyngeal carcinoma (NPC). EBV is etiologically linked with at least 8% of gastric cancer (EBVaGC) that comprises a genetically and epigenetically distinct subset of GC. Although we have a very good understanding of B cell entry and lymphomagenesis, the sequence of events leading to EBVaGC remains poorly understood. Recently, ephrin receptor A2 (EPHA2) was proposed as the epithelial cell receptor on human cancer cell lines. Although we confirm some of these results, we demonstrate that EBV does not infect healthy adult stem cell-derived gastric organoids. In matched pairs of normal and cancer-derived organoids from the same patient, EBV only reproducibly infected the cancer organoids. While there was no clear pattern of differential expression between normal and cancer organoids for EPHA2 at the RNA and protein level, the subcellular location of the protein differed markedly. Confocal microscopy showed EPHA2 localization at the cell-cell junctions in primary cells, but not in cancer cell lines. Furthermore, histologic analysis of patient tissue revealed the absence of EBV in healthy epithelium and presence of EBV in epithelial cells from inflamed tissue. These data suggest that the EPHA2 receptor is not accessible to EBV on healthy gastric epithelial cells with intact cell-cell contacts, but either this or another, yet to be identified receptor may become accessible following cellular changes induced by inflammation or transformation, rendering changes in the cellular architecture an essential prerequisite to EBV infection. KW - Organoids KW - ephitelial cells KW - gastrointestinal infections KW - cancers and neoplasms KW - Epstein-Barr virus KW - flow cytometry KW - epithelium Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259206 VL - 17 IS - 2 ER - TY - JOUR A1 - Kayisoglu, Özge A1 - Schlegel, Nicolas A1 - Bartfeld, Sina T1 - Gastrointestinal epithelial innate immunity-regionalization and organoids as new model JF - Journal of Molecular Medicine N2 - The human gastrointestinal tract is in constant contact with microbial stimuli. Its barriers have to ensure co-existence with the commensal bacteria, while enabling surveillance of intruding pathogens. At the centre of the interaction lies the epithelial layer, which marks the boundaries of the body. It is equipped with a multitude of different innate immune sensors, such as Toll-like receptors, to mount inflammatory responses to microbes. Dysfunction of this intricate system results in inflammation-associated pathologies, such as inflammatory bowel disease. However, the complexity of the cellular interactions, their molecular basis and their development remains poorly understood. In recent years, stem cell-derived organoids have gained increasing attention as promising models for both development and a broad range of pathologies, including infectious diseases. In addition, organoids enable the study of epithelial innate immunity in vitro. In this review, we focus on the gastrointestinal epithelial barrier and its regional organization to discuss innate immune sensing and development. KW - regionalization and organoids KW - immunity KW - gastrointestinal tract Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265220 VL - 99 IS - 4 ER - TY - INPR A1 - Bartfeld, Sina T1 - Modeling infectious diseases and host-microbe interactions in gastrointestinal organoids T2 - Developmental Biology N2 - Advances in stem cell research have allowed the development of 3-dimensional (3D) primary cell cultures termed organoid cultures, as they closely mimic the in vivo organization of different cell lineages. Bridging the gap between 2-dimensional (2D) monotypic cancer cell lines and whole organisms, organoids are now widely applied to model development and disease. Organoids hold immense promise for addressing novel questions in host-microbe interactions, infectious diseases and the resulting inflammatory conditions. Researchers have started to use organoids for modeling infection with pathogens, such as Helicobacter pylori or Salmonella enteritica, gut- microbiota interactions and inflammatory bowel disease. Future studies will broaden the spectrum of microbes used and continue to establish organoids as a standard model for human host-microbial interactions. Moreover, they will increasingly exploit the unique advantages of organoids, for example to address patient-specific responses to microbes. KW - gastrointestinal disease KW - salmonella KW - microbiota KW - inflammatory bowel disease KW - organoid culture KW - helicobacter KW - rotavirus KW - norovirus Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-138788 UR - http://www.sciencedirect.com/science/article/pii/S0012160616304602 SN - 0012-1606 N1 - This is the accepted version of the following article: Bartfeld, Sina, Modeling infectious diseases and host-microbe interactions in gastrointestinal organoids, Developmental Biology, 2016, 420, 2, 262-270. http://dx.doi.org/10.1016/j.ydbio.2016.09.014 ER - TY - JOUR A1 - Bartfeld, Sina T1 - Realizing the potential of organoids — an interview with Hans Clevers JF - Journal of Molecular Medicine N2 - No abstract available. KW - organoids KW - interview Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235804 SN - Journal of Molecular Medicine VL - 99 ER -