FIGURE 2 from Single-cell Profiling Uncovers a Muc4-Expressing Metaplastic Gastric Cell Type Sustained by Helicobacter pylori-driven Inflammation

Hp+KRAS+ mice have abundant metaplastic pit cells that express the intestinal mucin Muc4. A, The normalized expression of the indicated metaplasia and dysplasia genes is given for the cells from UMAP #2 (Fig. 1C). Asterisks indicate metaplastic pit cells. B, The estimated proportion of cells from the scRNA-seq experiment that were assigned to the indicated pit cell clusters is shown. Each datapoint shows the total number of estimated cells of that subcluster for the given treatment group, reported as the percentage of all cells from that treatment group in UMAP #2. Error bars represent the confidence interval that a given percentage of cells would be identified as the given cluster type based on their observed distribution. C, The contour plots show Muc5Ac (x-axis) and Muc4 (y-axis) expression in the indicated pit cell clusters from UMAP #2. Expression is given as arbitrary units and negative values are due to data scaling for visualization purposes. D, Gene set enrichment analysis was performed to assess biological pathways and processes enriched in pit_2, pit_6, and pit_8 cells relative to the five other pit cell clusters, using Hallmark, KEGG, and GO pathway datasets from the MSigDB database. E and F, ISH was used to detect the intestinal mucin Muc4 (brown) in gastric corpus tissue (counterstained with hematoxylin, blue) from the indicated treatment groups at 12 weeks. E, Representative images are shown. Scale bars, 100 μm. Arrows show Muc4 expression at the epithelial surface in KRAS− samples. F, Tissues were scored in a blinded fashion. N = 5 independent experiments were performed with n = 3–8 mice per group. Data represent actual values from each individual mouse and bars indicate the median values.