TGLU Talk: SIREN – Stomach inflammation and its impact on related early neoplasia by Dr Jan Bornschein, Oxford
Background: Helicobacter pylori (H. pylori) is classified as class I carcinogen being the main risk factor for gastric cancer. During the last years, several studies have utilised single cell sequencing techniques to create a better understanding of the molecular background of gastric cancer and the link between malignant neoplastic and preneoplastic conditions. However, the changes caused by H. pylori in the initial stages of chronic-active inflammation have not yet been fully analysed at single cell level.

Methods: We applied RNA single and ATAC sequencing on a cohort of n=12 patients (50% H. pylori positive). Samples from further 8 patients were sent for a pilot of spatial transcriptomics using the 10X XENIUM assay. Organoids were grown from biopsies to be then further transferred into 2D mucosoid culture models. These were challenged with H. pylori, CagA as key virulence factor and ADP Heptose as main active effector of CagA positive strains.

Results: We identified 2 epithelial cell populations that emerge in direct response to the infection. One of these consists of cells that are located at the isthmus (proliferative) segment of the gastric gland. These cells show a strongly enhanced immune reaction, with increased expression of cytokines and chemokines that further orchestrate both the local immune response as well the inflammatory field effect in the stomach in general. The other population shows cells that are more localised in the foveola region of the gastric glands. These cells are more enriched for gene signatures involved in metabolic processes, energy recruitment as well as those regulating actin filament organisation and cell-cell adhesion factors. Chromatin accessibility assays confirm that some of the transcriptional regulation of these cell populations is facilitated on epigenetic level. The impact of H. pylori on the expression of key genes was confirmed in the cell model.

Outlook: Among other findings the key focus lies on the characterisation of the two epithelial cell populations that emerge as a result of H. pylori infection. This includes the analysis of their cellular origin and further trajectory in view of the development of further (pre)neoplastic changes, and of the interaction with stromal and immune cell compartments. Further work is planned utilising the ex vivo cell model as well as submission of an extended cohort for spatial transcriptomics.
Date: 24 April 2025, 16:30
Venue: John Radcliffe Hospital - Main Building, Headington OX3 9DU
Venue Details: JR, GPEC Seminar Room 4B, Level 3 JR Hopital, Oxford
Speaker: Dr Jan Bornschein (University of Oxford)
Organiser: Professor Holm Uhlig (University of Oxford)
Organiser contact email address: verity.daies@ndm.ox.ac.uk
Host: Dr Michael Fitzpatrick
Part of: TGLU Seminars
Booking required?: Not required
Audience: NHS & University Welcome
Editor: Verity Davies