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Identifying tumor type and cell type-specific gene expression alterations in pediatric central nervous system tumors
Min Kyung Lee1, Nasim Azizgolshani1,2, Joshua A Shapiro3
1Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
Abstract:
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 collect single nuclei RNA-seq data from 84,700 nuclei of 35 pediatric CNS tumors and three non-tumoral pediatric brain tissues and characterize tumor heterogeneity and transcriptomic alterations. We distinguish cell subpopulations associated with specific tumor types including radial glial cells in ependymomas and oligodendrocyte precursor cells in astrocytomas. In tumors, we observe pathways important in neural stem cell-like populations, a cell type previously associated with therapy resistance. Lastly, we identify 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. Here we address current gaps in understanding single nuclei gene expression profiles of previously under-investigated tumor types and enhance current knowledge of gene expression profiles of single cells of various pediatric CNS tumors.
Insights
This study analyzes pediatric central nervous system (CNS) tumors using single nuclei RNA sequencing. Findings reveal cell subpopulations and gene expression alterations, suggesting new therapeutic targets for these rare pediatric brain cancers.
Area of Science:
- Oncology
- Neuroscience
- Genomics
Background:
- Pediatric central nervous system (CNS) tumors are the primary cause of cancer-related death in children.
- Limited research exists on targeted therapies for pediatric CNS tumors due to their low prevalence.
- Patients with pediatric CNS tumors face a higher risk of developing secondary cancers.
Purpose of the Study:
- To characterize tumor heterogeneity and transcriptomic alterations in pediatric CNS tumors.
- To identify cell subpopulations within different pediatric CNS tumor types.
- To discover potential cell type-specific therapeutic targets for pediatric CNS tumors.
Main Methods:
- Single nuclei RNA sequencing (snRNA-seq) was performed on 84,700 nuclei from 35 pediatric CNS tumors and 3 non-tumoral pediatric brain tissues.
- Transcriptomic profiles were analyzed to identify cell subpopulations and gene expression patterns.
- Differential gene expression analysis was conducted comparing tumor and non-tumoral tissues, accounting for cell type variations.
Main Results:
- Distinct cell subpopulations were identified, including radial glial cells in ependymomas and oligodendrocyte precursor cells in astrocytomas.
- Pathways associated with neural stem cell-like populations, linked to therapy resistance, were observed in tumors.
- Transcriptomic alterations specific to pediatric CNS tumor types were identified compared to non-tumoral tissues.
Conclusions:
- The study provides valuable insights into the single-cell gene expression profiles of pediatric CNS tumors.
- Identified cell subpopulations and transcriptomic alterations offer potential targets for novel, cell type-specific therapies.
- This research addresses knowledge gaps and enhances understanding of pediatric brain tumor biology.
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