PTPS-06SINGLE-CELL TRANSCRIPTOME ANALYSIS IN PEDIATRIC HIGH-GRADE GLIOMA

Human tumors are complex systems containing cells with diverse phenotypes, genotypes and epigenetic states; but current treatment strategies and models do not adequately reflect tumor composition in patients. High-grade gliomas are particularly heterogeneous tumors and currently represent the most common cause of cancer-related death in children. Increasing evidence indicates that treatment failure and resistance are at least in part due to this heterogeneity. We used single-cell RNA sequencing (scRNA-seq) to profile the transcriptome of thousands of single cells in pediatric high-grade glioma and reconstructed their cellular architecture. We found restricted expression of neural stem/progenitor expression programs in distinct subsets of cells, and observed that cellular programs evolve during genetic evolution. This suggests that both genetic and superimposed developmental programs contribute to tumor heterogeneity. These results provide unparalleled insight into the cellular composition of pediatric high-grade gliomas at the level of single-cell resolution, and open up new avenues for discovering novel therapeutic targets.