Fig. 5: ETMR altered the fate determination of RG subpopulations in the FBO, supporting their differentiation into pericytes through WNT-TGFB-PDGFR signaling.

A, B ETMR altered the fate determination of non-malignant RG subpopulations in either the mETMR-FBO (A) or hETMR-FBO (B) compared to the FBO controls. RG clusters enriched in vascular development GO terms are referred to as RG-angio, while those enriched in PC marker genes are termed RG-PC. Bar graphs are color-coded by condition. C Monocle pseudotime trajectory of RG cells from the mETMR-FBO dataset illustrates differentiation path from RG-to-PC. Cells are color-coded by pseudotime. Arrows highlight the trajectory from early RG subpopulations to RG-PC. Dashed lines mark the clusters included in the trajectory analysis described in (D–G). D UMAP signature plots of transitional programs involved in RG-to-PC differentiation show that RG cells in the cyNESC program first undergo a mesenchymal (MES) transition, which further progress into a PC differentiation program. E Line plots illustrate gene expression trends across pseudotime for selected genes differentially expressed along the trajectory. Genes are grouped into functional programs, indicated by boxed sections that mark their association with specific pseudotime stages. Lines represent non-linear smoothed gene expression trajectories (LOESS fit); black lines indicate the estimated central tendency, and gray shaded areas denote the 95% confidence interval based on standard error. F Heatmap shows expression scores of marker genes representing signaling pathways that are differentially upregulated in RG clusters involved in the RG-to-PC trajectory. Pathways were identified via ToppGene analysis. G Schematic of cell types and signaling pathways involved in RG lineage conversion to PC. Created with BioRender.com. H Diagram of predicted L_R interactions (from CellPhoneDB/InterCellar) involved in promoting RG-to-PC differentiation (see also Supplementary Fig. S17). Source data of (A, B) are provided as a Source Data file. Sample type symbols in (A–F, H) created with BioRender.com.