Fig. 1: Establishment of a CRC PDO library that recapitulates the heterogeneity of the primary tumors. | Nature Communications

Fig. 1: Establishment of a CRC PDO library that recapitulates the heterogeneity of the primary tumors.

From: Epigenomic landscape of human colorectal cancer unveils an aberrant core of pan-cancer enhancers orchestrated by YAP/TAZ

Fig. 1

a Schematic depicting the generation of a patient-derived organoid (PDO) library from primary CRC tissues and its subsequent morphological, transcriptomic, and epigenomic profiling. b Genetic and molecular classification of primary tumors revealed the heterogeneity of the organoid library. CRC patients are classified based on the consensus molecular subtypes2, the CRC intrinsic classifier3, and the CRCassigner14. MSI Microsatellite instable (blue), MSS Microsatellite stable (red), CMS Consensus molecular subtypes, CRIS CRC intrinsic classifier. c Representative confocal images of 3D immunofluorescence whole-mount analysis on human CRC PDOs. Different markers of colon cell types are shown: polarity and structure (F-Actin, first row), the epithelium (EpCAM, first row), proliferation (Ki67, first row), absorptive cells (FABP1, second row), enteroendocrine cells (CHGA, second and third row), goblet cells (MUC2, third row), and top epithelial crypt cells (KRT20, third row). The fourth row provides an enlargement of the boxed area in the third row. Scale bars, 100 µm. d PCA on normalised gene counts from RNA-seq data distinguished normal colon mucosa, primary tumor, and PDOs. e, Venn diagram showing the number of concordant expressed genes between tumors and PDOs. Mean log2 normalized gene counts between primary tumors and PDOs were well correlated (Pearson correlation). See Supplementary Fig. 1b–d. f Hierarchical clustering analysis using differentially expressed genes (DEG, two-sided adjusted P-value ≤ 0.01 by Wald test with Benjamini–Hochberg false discovery rate correction) between tumor and normal colon tissues clustered PDOs together with parental tumors. Tissue populations and patients are represented by color-coded bars above the heatmap. g PDOs are enriched in gene signatures of CRC clinical specimen15. GSEA on the ranked list of genes from the comparison between PDOs and normal colon tissue with the normalized enrichment score (NES) and nominal P-value using 1000 permutations reported.

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