Fig. 6: IFN-I-driven chromatin remodeling.
From: Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B
a–d, ATAC–seq (a–c) and RNA-seq (d) analysis in PAR or CD44H MCA205 cells. Heatmap illustrating global open (O) or closed (C) genes and representative gene subgroups in PAR/P and CD44H/H are shown in a, representative Kdm1b loci within CPOH group in b, TF binding motifs enriched more than twofold in PAR (black) or CD44H (purple) cells (x-axis, TF motif enrichment log FC in target/nontarget cells; y-axis, significance enrichment level) in c, and GO network analysis of upregulated (red) and downregulated (blue) genes in CD44H cells (nodes, enriched GO terms, node size, false discovery rate-adjusted enrichment P value (q value)) in d. e, Multiparametric flow cytometry analysis showing CD44H cell percentages upon OXP or OXP + TCP. Mean ± s.e.m. and individual data points. Number of biologically independent samples collected over two independent experiments is reported. f, Schematic experimental protocol of in vivo KDM1B inhibition and multiparametric flow cytometry analysis of CD44H and CD8+TIM3+ percentages in tumors from mice upon DOX or DOX + TCP treatment. Mean ± s.e.m. and individual data points for 12 and 15 mice per group from three experimental replicates. g, In vivo MCA205 tumor growth control in mice treated as illustrated. Tumor growth curves (mean tumor surface ± s.e.m. for 15 and 16 mice per group from three experimental replicates) and tumor-free mice percentages are reported. h, Ex vivo multiparametric flow cytometry analysis of CD44H percentages in PAR and Kdm1b-overexpressing (Kdm1bOVER) MCA205-derived tumors. Mean ± s.e.m. and individual data points for 12 mice per group from two experimental replicates. i–k, In vivo evaluation of Kdm1bOVER and Kdm1b-depleted (Kdm1bKD) MCA205 metastatic potential (i), DOX-based therapeutic response (j) and tumorigenicity (k) in C57Bl/6J (i–k) and NSG (k) mice. Mean ± s.e.m. and individual data points for 6 mice per group from two experimental replicates (i, j), and for 12 and 6 mice per group from two experimental replicates (k). See also Extended Data Figs. 5 and 6. c, One-sided binomial test. e, Ordinary one-way ANOVA test with Bonferroni’s correction. f, Kruskal–Wallis test with Dunn’s multiple comparisons. g,k,j, Ordinary two-way RM ANOVA test with Bonferroni’s correction (g) and log-rank (Mantel–Cox) test (g,k). h, Two-tailed Mann–Whitney test compared with PAR. i, Unpaired two-sided Student’s t-test with Welch’s correction.
