Fig. 3: Transcriptional deregulation in TP53-deficient gastric organoids.
From: Deterministic evolution and stringent selection during preneoplasia
a, Experimental overview of longitudinal scRNA-seq profiling of gastric organoid cultures. WT and replicate TP53–/– HGOs were sampled at multiple time points (early, about 100 days, orange; mid, about 320 days, blue; late, about 770 days, purple) and subjected to scRNA-seq. b, Dot-plot depicting estimated growth curve derivatives and growth fold change (FC) from previous time points for each culture over time (interpolated passage number). c, Uniform manifold approximation and projection (UMAP) visualizations coloured according to culture (left) and time point (right) for D1, depicting 13,984 cells. d, Dot-plot depicting the expression of selected marker genes for individual cultures and time points. Coloured bars highlight (1) marker genes associated with normal gastric and intestinal cell types, (2) genes upregulated in gene expression profiling interactive analysis (GEPIA) of GC and (3) others of functional relevance. PMCs, MUC5AC, TFF1, dark yellow; GMCs, MUC6, TFF2, light blue; proliferative cells, MKI67, purple; neck-like cells, PGC, LYZ, orange; mucosal stem cells, OLFM4, turquoise; enterocytes, FABP1, VIL1, olive; goblet cells, TFF3, WFDC2, MUC5B, CDX2, green; GEPIA top 12 genes, CEACAM5, CEACAM6, CLDN3, CLDN4, CLDN7, REG4, MUC3A, MUC13, PI3, UBD, AOC1, CDH17, black; other, TP53, APC, CDKN2A, FHIT, red. e, UpSet plot representing shared differentially up- (left) and downregulated genes (right) across donors and cultures (P < 0.05, Bonferroni corrected two-sided Wilcoxon rank-sum test). f, GSEA heatmap for MsigDB Hallmark gene sets showing pathways most significantly altered for each culture (Kolmogorov–Smirnov statistic, Benjamini–Hochberg adjusted, two-sided). GSEA score is indicated (dot size) and coloured according to the directionality of expression profiles (up, red; down, blue). Image of stomach in a is from Servier Medical Art, CC BY 3.0.
