Fig. 6. Epigenetically active subpopulations raise cellular heterogeneity in MYC tumor cells.

A UMAP indicates the expression of 98 cell cycle-related genes⁴⁸ in RT tumors from different MYC subtypes. Zoom-in boxes depict TCs with newly added subclusters to highlight cells in G2/M or S phase (subclusters in gray are further referred to as mitotic cells). B Heatmaps show shared biological processes of TCs in G2/M or S phase across MYC subtypes. C GO term analysis of shared upregulated DEGs (upregulated in mitotic TCs) derived from the comparison between mitotic tumor cells and tumor cells expressing G1 phase-specific genes. Only significantly enriched cellular component (CC) terms are shown (x-axis, −log10 scale). Differential expression analysis used MAST algorithm⁸⁸. Statistically significant genes were considered having a q-value <0.05 (Bonferroni correction). Functional annotation was performed using ToppGene Suite⁸⁷ (with statistical method as probability density function) considering GO terms enriched with an adjusted p-value (FDR) < 0.05. D Dot plots depict the relative gene expression of distinct epigenetic modifiers derived from a direct comparison between TCs of each MYC subtype. The fraction of cells (black dots) and the average scaled expression (blue scales) are shown. E Global methylation levels are shown for PGCs (n = 13 biologically independent samples, ranging week7-week19) and ATRT-MYC samples (n = 33 biologically independent samples). For each box, the lower and upper bounds represent the 25th and 75th percentiles; the center corresponds to the 50th percentile (median). The upper whisker extends to the largest value no further than 1.5 * IQR from the bound (where IQR is the interquartile range, or distance between the 25th and 75th percentiles). The lower whisker extends to the smallest value at most 1.5 * IQR of the bound. Data beyond the end of the whiskers are called outlying points and are plotted individually. Source data are provided as a Source data file.