Fig. 2

Heterogeneity in the chromatin accessibility of ESCC epithelial cells. A UMAP plot of all epithelial cells colored by the cell subtype according to the scATAC-seq data. B UMAP plot of all epithelial cells colored according to inferCNV type in the scATAC-seq data. C Volcano plots showing differential epithelial peaks in malignant and nonmalignant cells. A total of 3709 upregulated peaks and 6030 downregulated peaks were identified. The log2mean is the logarithm of the arithmetic mean of the absolute value of the deviation between genescore and the mean of genescore. D Scatter plots showing DEGs between scATAC and scRNA-seq data from malignant and nonmalignant epithelial tissues in ESCC. Genes with log2FC > 0.25 in both the scATAC-seq and the scRNA-seq data were considered upregulated genes; those whose log2FC < -0.25 in both the scATAC-seq and the scRNA-seq data were considered downregulated genes. E The UMAP plots are colored according to log-normalized gene scores, indicating the accessibility of cis-regulatory elements linked to the indicated gene (CCND1 and KRT13) from the scATAC-seq data (upper). The UMAP plots show all epithelial cells colored according to gene expression (CCND1 and KRT13) from the scRNA-seq data (lower). F Browser track showing the accessibility profile at the CCND1 locus across malignant and nonmalignant cells. G UMAP plots of all epithelial cells colored by inferCNV type based on the scRNA-seq dataset. H KEGG signaling pathway diagram of DEGs associated with regulatory elements. The horizontal axis represents -log10(P-value), and the color indicates the number of genes involved. I Vein plot showing the intersection of DEGs in scATAC-seq (Log2FC > 0.25), scRNA-seq (Log2FC > 0.25), RNA-seq (KYSE150 vs. HEEC, Log2FC > 1), and RNA-seq (ESCC vs. peritumor clinical samples, Log2FC > 1) data from malignant cells and nonmalignant cells (left). Browser track showing the accessibility profile at the SERPINH1 locus across malignant and nonmalignant cells. The putative cancer-specific dRE of SERPINH1 is highlighted by a light yellow shadow (middle). Matching of the scRNA-seq expression of SERPINH1 is shown for all subclusters (right). J The UMAP plot is colored according to log-normalized gene scores, showing the accessibility of cis-regulatory elements linked to SERPINH1 based on the scATAC-seq GeneScoreMatrix