Extended Data Fig. 8: p53 regulates chromatin accessibility noise in lung adenocarcinoma.
From: Thymic epithelial cells amplify epigenetic noise to promote immune tolerance
a, UMAP of merged scATAC-seq data from lung adenocarcinomas44 (LUAD) in p53-KO, p53-WT and p53-Hyper mice colored by genotype. b, Cluster annotations overlayed on UMAP of merged scATAC-seq data from (a). c–f, LUAD progression depicted by aggregate expression of genes defining alveolar type-2 (AT2) lung epithelial state43 (c), mixed alveolar type-1 and type-2 lung epithelial state43 (d), embryonic liver state43 (e) or epithelial-to-mesenchymal transition (EMT) state43 (f) overlayed on scATAC-seq UMAP from (b). g, Nkx2-1 gene expression levels overlayed on scATAC-seq UMAP from (a). h, Prevalence of NKX2.1-binding motifs across accessible LUAD genomes (chromVAR deviation scores) overlayed on scATAC-seq UMAP from (a). i, Runx2 expression overlayed on scATAC-seq UMAP from (b). j, Prevalence of RUNX2-binding motifs across accessible LUAD genomes (chromVAR deviation scores) overlayed on scATAC-seq UMAP from (a). k, Fraction of indicated LUAD clusters represented by each genotype. l, Fraction of scATAC-seq fragments within scATAC-seq peaks (WIP) overlayed on UMAP from (b). m, Fraction of mononucleosomal scATAC-seq fragments overlayed on UMAP from (b). n,o, Bar plots depicting WIP fraction (n) or the fraction of mononucleosomal scATAC-seq fragments (o) within cells (n = 5,556: C1 = 813, C2 = 745, C3 = 153, C4 = 1091, C5 = 495, C6 = 434, C7 = 369, C8 = 1456) of indicated genotypes across annotated LUAD clusters defined in (a–j). Error bars represent mean ± SEM. P-values from one-sided Mann-Whitney U-tests comparing p53-cHyper or p53-cKO cells to WT cells within each cluster.
