FIGURE 1 from Single-cell Profiling Uncovers a <i>Muc4</i>-Expressing Metaplastic Gastric Cell Type Sustained by <i>Helicobacter pylori</i>-driven Inflammation

Abstract

<p>Gastric scRNA-seq reveals expansion of pit cell populations in <i>Hp</i>+KRAS+ mice. <b>A,</b> Overview and experimental timeline for mouse experiments, created with BioRender.com. TMX, tamoxifen. <b>B–F,</b> Mice ± <i>Hp</i> infection and ± constitutively active KRAS induction were used for gastric scRNA-seq. Corpus single-cell suspensions were prepared from: one <i>Hp</i>−KRAS+ and one <i>Hp</i>+KRAS+ mouse at 6 weeks; and at 12 weeks, three <i>Hp</i>−KRAS− and two <i>Hp</i>+KRAS− (each pooled into one sample), one individual (never cryopreserved) and two pooled <i>Hp</i>−KRAS+ mice, and one individual (never cryopreserved) and two pooled <i>Hp</i>+KRAS+ mice. <b>B,</b> Cluster analyses followed by UMAP visualization of the entire dataset yielded 25 clusters, including epithelial and immune cell types, which were manually annotated on the basis of gene expression. Endocrine, enteroendocrine cell; cDC, conventional dendritic cell; RBC, erythrocyte/reticulocyte; pDC, plasmacytoid dendritic cell. <b>C,</b> Cells from the 12 week timepoint in the central epithelial cell megacluster, outlined with the dotted line in B, were subjected to reclustering followed by UMAP visualization, yielding 14 clusters that were manually annotated on the basis of gene expression. <b>D,</b> The normalized expression of marker genes for the indicated gastric epithelial cell types is shown for the 14 epithelial clusters from UMAP #2 in C. <b>E,</b> The estimated proportion of each of the 14 epithelial clusters detected in the pilot scRNA-seq experiment in the indicated treatment groups at 12 weeks is shown (rows add to 100%). ND, cell cluster was not detected in the indicated treatment group. <b>F,</b> The distribution of pit cell clusters within each treatment group in E is shown.</p>