Tumor type and cell type-specific gene expression alterations in diverse pediatric central nervous system tumors identified using single nuclei RNA-seq.

Central nervous system (CNS) tumors are the leading cause of pediatric cancer death, and these patients have an increased risk for developing secondary neoplasms. Due to the low prevalence of pediatric CNS tumors, major advances in targeted therapies have been lagging compared to other adult tumors. We collected single nuclei RNA-seq data from 35 pediatric CNS tumors and three non-tumoral pediatric brain tissues (84,700 nuclei) and characterized tumor heterogeneity and transcriptomic alterations. We distinguished cell subpopulations associated with specific tumor types including radial glial cells in ependymomas and oligodendrocyte precursor cells in astrocytomas. In tumors, we observed pathways important in neural stem cell-like populations, a cell type previously associated with therapy resistance. Lastly, we identified transcriptomic alterations among pediatric CNS tumor types compared to non-tumor tissues, while accounting for cell type effects on gene expression. Our results suggest potential tumor type and cell type-specific targets for pediatric CNS tumor treatment. In this study, we address current gaps in understanding single nuclei gene expression profiles of previously uninvestigated tumor types and enhance current knowledge of gene expression profiles of single cells of various pediatric CNS tumors.