Figure 4 from Single-Cell RNA Sequencing Unifies Developmental Programs of Esophageal and Gastric Intestinal Metaplasia

Abstract

<p>E-GM and atrophic gastritis share early features of developing IM. <b>A,</b> UMAP of columnar cells of gastric cell types (NGC and NGB, top left), E-GM (top right), and atrophic gastritis (NAG and CAG, bottom left) with cell-type annotation highlighted. Bottom right, UMAP with clusters 6 and 16 (identified during reclustering of columnar cells and overlapping gastric neck cells) highlighted. EE, enteroendocrine. <b>B,</b> Stacked bar chart of tissue contribution to the cells assigned to clusters 6 and 16. <b>C,</b> Gene set enrichment analysis (GSEA) using the C3 gene set database of differentially expressed genes between neck-like cells from E-GM and NGC samples. HNF4A- and MYC-related pathways are highlighted. The differential analysis was done between E-GM cells and NGC + NSCJ neck-like cells with each patient treated as an individual replicate. NES, normalized enrichment score. <b>D,</b> GSEA using the C3 gene set database of differentially expressed genes between NAG/CAG and NGC/NGB/NSCJ sample neck-like cells. AP-1–related pathways are highlighted. The differential analysis was done between cluster 16 cells (including NAG, CAG, and E-GM cells) and cluster 6 (including NGC + NGB + NSCJ neck-like cells) with each patient treated as an individual replicate. <b>E,</b> Venn diagram demonstrating the overlap between genes enriched in the comparison of atrophic gastritis (NAG and CAG) and normal gastric samples or E-GM and normal gastric samples. Bottom left: bubble plot of top 25 expressed genes shared between the comparison. Bottom right, violin plots of selected genes. <b>F,</b> WGS-based analysis of E-GM and BE-IM. Top, mutational burden [single-nucleotide variants/megabase (SNV/Mb)] of NGC, E-GM, and BE-IM samples. Bottom, distribution of COSMIC SNV signatures in the E-GM and BE-IM samples.</p>