Fig. 3. Distinct epigenetic regulation and biological processes associated with tumor epithelial cells.

a UMAP plot of scATAC-Seq for both the tumor epithelia and normal epithelia regions within BCC21. b Feature plot of the GeneScoreMatrix for GLI1 for human BCC21 scATAC-Seq data as shown in Fig. 3a. c The differential marker features from the scATAC-Seq data of human BCC21 between tumor epithelia and normal epithelia populations. d UMAP plots of scRNA-Seq (left) and scATAC-Seq (right) data integration for the tumor epithelia and normal epithelia populations of human BCC21. e GO analysis for marker genes from (1) scRNA-Seq (top) and (2) scATAC-Seq (bottom) of C1 vs. C2. f Edu% of Ly6d⁺ cells from either normal mouse skin organoids or tumor organoids. Each point represents Edu% from distinct organoids (n = 4) derived from BCCs or normal mouse skin from different mice. g Heatmap indicating the enriched motifs in the various clusters from normal and BCC cells. h Feature plot of the MotifMatrix for various motifs identified in Fig. 3g superimposed onto the different clusters from the normal and BCC cells to indicate the specificity of enrichment. i Feature plot highlighting expression of the various genes (JUNB, SMARCC1, FOXN3, and RUNX1), whose motifs were identified in h. j Brightfield images of organoids from mouse BCC tumors that were treated with SMOⁱ, Runx1ⁱ, or SMOⁱ with Runx1ⁱ. Inhibitor treatments were at 1 μM. k Quantification of the organoid area after growth with the various drugs from distinct primary tumors (n = 4). l Diagram of the CRISPR strategy to target Foxn3 and Runx1 in ASZs. m Gene expression of Gli1, Tacstd2, and Lypd3 in wildtype and different clones of Foxn3-KO and Runx1-KO cells. Each point represents technical replicates (n = 4) of gene expression values of the specified gene normalized to Gapdh. Length of each scale bar is noted in figure. f, k, and m error bars represent mean ±SD. f, k p values were calculated using unpaired, two-tailed t test. Source data are provided as a Source Data file.