Fig. 4: GSC-specific dependencies uncovered by neoloop analyzes and simulations.

a Exemplary Hi-C contact map from G148 around a translocation breakpoint involving the MYC locus. Enhancer-promoter neoloops forming across the breakpoint are indicated (blue circles) and aligned to RNA-seq, H3K27ac, and CNV tracks. Absence of neoloops in G394 (below), where no translocation occurs, provides a control. b Plot showing mean (line) ±SEM GSC-specific MYC expression (circles) in cells with (orange; n = 1) or without the chr8:chr12 translocation (gray; n = 9) or in astrocytes (black; n = 2). Source data for this panel are provided as a Source Data file.c, Plots showing the percentage of cells ±SD staining positive for MYC or Ki-67 in untreated (red) or EN4-treated MYC-high G148 (green) from n = 4 independent experiments; treatment of the MYC-low G62 provides a control. *: P = 0.038 (for MYC) and 0.021 (for Ki-67), unpaired two-sided Student’s t-test. Source data for this panel are provided as a Source Data file. d As in panel (c) but showing the percentage of cells ±SD positive for TUNEL staining from n = 4 independent experiments. *: P = 0.00025, unpaired two-sided Student’s t-test. Source data for this panel are provided as a Source Data file. e Heatmaps showing correlation of each class of polymer beads with H3K27ac and RNA-seq data from G148 that carries the chr8:chr12 translocation (left) or G394 that does not (right). Classes with a correlation of >0.2 are shown. f Left: Contact maps from Hi-C (top) or simulations (bottom) around the translocation breakpoint in G148 are shown aligned to polymer bead classes. Enhancer-promoter neoloops forming across the breakpoint are indicated (blue circles). Right: As in the left hand-side panel, but for G394 that does not carry the translocation. g Representative 3D renderings of the two major configurations resulting from chr8:chr12 ecDNA translocation involving the MYC locus. Beads from binding classes 1, 7, and 11 that best predict folding are color-coded as in panel d, and differential MYC-enhancer interactions indicated (yellow halo).