American Association for Cancer Research
crc-23-0142_fig5.png (2.05 MB)

FIGURE 5 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

The EGFR ligand amphiregulin is another marker of metaplastic pit cells. A, The heat map shows the normalized expression of the top 25 genes that are most significantly differentially expressed between Muc4-expressing (bottom) and non-expressing (top) metaplastic pit cells (pit_2, pit_6, and pit_8 cells). Genes are ranked from left to right in order of statistical significance. B,Muc4 and Areg coexpression was assessed for each cluster in UMAP #2. Only the five indicated clusters had a Pearson correlation P value < 0.05. The expression of Muc4 and Areg in counts per 10,000 reads is plotted for each cell in the given cluster. Trend lines are plotted and shading indicates the confidence interval of the linear estimation. C, Fluorescent ISH was used to detect Muc4 (green) and Areg (magenta) from representative mice at 12 weeks; DAPI (blue) indicates nuclei and single channel images are shown in grayscale. Scale bars, 100 μm.


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)



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.