Fig. 6: Systematic analysis of tumor-promoting receptor–ligand interactions.
a, Network graph showing the interactions between receptors (rectangles) and ligands (ellipses) across our single-cell ETMR cohort (n = 6 samples), as inferred using genome-wide CellPhoneDB analysis performed separately on each sample. The different fill colors indicate the cell-type specificity of receptors and ligands. Line width indicates the number of samples in which the interaction was detected (P < 0.05). A larger version of the network graph is shown in Extended Data Fig. 8a,b. b, The network graph shows the FGFR signaling subnetwork. Receptors are specifically expressed in NSC-like tumor cells, while several ligands are specific to neuron-like cells. Line width indicates the number of samples in which the interaction was detected (P < 0.05). c, Network graph showing the Notch signaling network. Receptors are specifically expressed in NSC-like tumor cells, while Delta ligands (DLL1, DLL3, DLL4) are specific to intermediate cells. d, t-SNE representation of n = 2,520 malignant ETMR cells colored according to the mean relative expression of FGF receptors (left) and ligands (right). e, t-SNE representation of n = 2,520 malignant ETMR cells colored according to the mean relative expression of Notch receptors (left), Delta ligands (center) and Jagged ligands (right). f, Heatmap showing cell confluency after FGF growth factor stimulation in BT183 ETMR cells over a time course of 138 h. Cells were seeded as 2D cultures and cell growth was followed by live-cell microscopy. Four biological replicates were analyzed and different FGF ligands were grouped according to subfamilies. Statistical analysis was performed using a one-way ANOVA of the AUCs. Padj values are given. The results of n = 4 biological replicates are shown. g, Heatmap showing cell confluency after soluble Delta ligand stimulation over a time course of 183 h. Four biological replicates were analyzed. Statistical analysis was performed using a one-way ANOVA of the AUCs. Padj values are given. The results of n = 4 biological replicates are shown. h, Heatmaps showing the relative expression of refined signature genes (n = 100) per ETMR cell type in n = 3 PDX models. Top, Cell-type assignment and cells in a cycling state are indicated. i, Representative H&E and IF staining of BT183 PDX for the indicated markers. Scale bars, 300 µm. This experiment achieved reproducible results in three biological replicates. The dashed box in the H&E image indicates the tumor area shown in the IF staining below.
