Fig. 2: Colonic epithelial identity is perturbed after Atrx loss.

a, Heatmap of RNA-seq data from AKP control and AKP Atrx^KO organoids with or without TGFβ treatment. Representative genes marking colonic epithelial, squamous and mesenchymal lineages are shown. log₂ fold change values relative to untreated AKP control organoids are indicated by the colour intensity. Genes of multiple lineages co-expressed in AKP Atrx^KO organoids are highlighted as ‘hybrid phenotype’. b, TissueEnrich analysis of genes upregulated and downregulated in AKP Atrx^KO organoids compared with AKP controls. Dashed line indicates P = 0.05. c, UMAP plot of AKP control (23,579 cells) and AKP Atrx^KO (25,757 cells) single cells coloured by genotype. d, UMAP plot coloured and numbered by cluster in AKP control and AKP Atrx^KO single cells. e, UMAP plots coloured by the expression of genes used for defining colonic differentiation and EMT in AKP control and AKP Atrx^KO single cells. Colour scale indicates expression levels. f, UMAP plot coloured by the expression of genes used for defining squamous differentiation in AKP control and AKP Atrx^KO single cells. Colour scale indicates expression levels. g, TissueEnrich analyses of genes enriched in single-cell RNA-seq clusters 4 and 15. Dashed line indicates P = 0.05. h, Dot plot of signature scores across all clusters coloured by the average expression and sized by the percentage of cells expressing the signature. Cluster 4 oesophagus and cluster 15 skin signatures are derived from TissueEnrich analyses. Significance was calculated using hypergeometric tests (one-sided) with Benjamini–Hochberg multiple-testing correction (b,g).