Extended Data Fig. 8: Mutation-induced environmental changes.
From: Tracing oncogene-driven remodelling of the intestinal stem cell niche
a, t-SNE representing immune cells from Confetti and Red2Onco mice. b, c, Heat maps representing differential expression (DE) patterns for mesenchymal (b) and immune (c) cells from Red2Onco and Confetti mice: top 300 genes or less (FDR < 0.05, pairwise t-test). Colour bar, averaged Z-scores of log2-transformed normalized UMIs. d, Secretion factor expression in stromal clusters for Confetti. In d, f, dot size denotes percentage of cells expressing gene; colour shows average expression. e, UMAPs showing expression of Bmpr1a and Fzd7 in epithelial cells. Colour bar, log2-transformed normalized UMIs. Inset from Fig. 3b. f, Dot plots showing expression of receptors upstream of BMP and WNT pathways for epithelial cells. g, h, Fractions of mesenchymal (g) and immune (h) cells in Red2Onco and Confetti mice. Data are mean ± s.e.m. Two-sided likelihood ratio test: *P < 0.05, **P < 0.01; n.s., statistically not significant (P > 0.05). i, Degree of transcriptomic change for immune cells estimated by cell-to-cell variability (PVAR) or separability of perturbed and unperturbed cells (PAUGUR). Dotted lines show −log10(0.01). Dot colour denotes cell type; dot shape shows Red2Onco. j, Enriched biological processes from gene ontology (GO) analysis of DE genes in STC2 of Red2-PIK3CAH1047R mice relative to Confetti. One-sided Fisher’s exact test. Dotted line, −log10(0.05). k, l, Heat maps representing DE genes and their numbers (in parentheses) for mesenchymal (k) and immune (l) cells in Red2Onco mice compared to Confetti. Colour bar, log2(fold change) (Supplementary Table 3). m, Volcano plot representing DE genes in STC2 of Red2-PIK3CAH1047R mice relative to Confetti. Two-sided pairwise t-test. Red dots, genes for biological processes in j. Vertical dotted lines, absolute value of log2(fold change) = 0.259; horizontal, −log10(0.05). n, Model of direct and indirect cross-talk between mutant and WT crypts in Red2Onco mice. BC, B cell; DC, dendritic cell; Mono, monocyte; MP1, 2, macrophage 1, 2; PLC, plasma cell; TC, T cell. For exact P values, see Source Data.
