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FIGURE 4 from Single-cell Profiling Uncovers a Muc4-Expressing Metaplastic Gastric Cell Type Sustained by Helicobacter pylori-driven Inflammation

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posted on 2023-09-06, 17:07 authored by Valerie P. O'Brien, Yuqi Kang, Meera K. Shenoy, Greg Finak, William C. Young, Julien Dubrulle, Lisa Koch, Armando E. Rodriguez Martinez, Jeffery Williams, Elizabeth Donato, Surinder K. Batra, Cecilia C.S. Yeung, William M. Grady, Meghan A. Koch, Raphael Gottardo, Nina R. Salama

Antibiotic eradication of Hp reverses metaplastic pit cell expansion. Muc4 and gastric inflammation were assessed 12 weeks after KRAS induction in the following groups: Hp−KRAS+ mice; Hp+KRAS+ mice; and Hp+KRAS+ mice treated with antibiotics (“abx”) from weeks 6 to 8. A, ISH was used to detect Muc4 (brown) in the corpus at 12 weeks and representative images are shown. Scale bars, 100 μm. B–E, IHC was used to detect the indicated immune cell populations in gastric corpus tissue at 12 weeks. Data are from N = 2 independent experiments with n = 5–10 mice per group. B, Representative images of the gastric corpus are shown. CD3 (yellow) indicates T cells, CD4 (red) indicates Th cells, CD8α (green) indicates cytotoxic T cells, F4/80 (gray) indicates macrophages and DAPI (blue) indicates nuclei. Higher magnification images of the boxed regions are shown in the second row. Scale bars, 100 μm. C–E, The indicated immune cell populations were detected by IHC and quantified in each mouse using HALO software in N = 2 experiments. Each datapoint is the average quantitation in two fields of view for an individual mouse and bars represent the medians. ***, P < 0.001; ****, P < 0.0001; Mann–Whitney U test; ns, not significant.

Funding

Gastric Cancer Foundation (GCF)

HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)

HHS | NIH | National Cancer Institute (NCI)

Cancer Research Institute (CRI)

American Association for Cancer Research (AACR)

History

ARTICLE ABSTRACT

Using a mouse model, we have delineated metaplastic pit cells as a precancerous cell type whose expansion requires Hp-driven inflammation. In humans, metaplastic pit cells show enhanced proliferation as well as enrichment in precancer and early cancer tissues, highlighting an early step in the gastric metaplasia to cancer cascade.