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Updated: Aug 8, 2025
Nuclei Isolation from Fresh Frozen Brain Tumors for Single-Nucleus RNA-seq and ATAC-seq
Published on: August 25, 2020
Tumor type and cell type-specific gene expression alterations in diverse 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 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.
Insights
Pediatric central nervous system (CNS) tumors are a leading cause of cancer death in children. This study reveals cell-specific gene expression changes in CNS tumors, identifying potential new therapeutic targets.
Area of Science:
- Neuro-oncology
- Genomics
- Pediatric oncology
Background:
- Central nervous system (CNS) tumors represent the primary cause of cancer-related mortality in children, with a notable risk of secondary malignancies.
- Limited progress in targeted therapies for pediatric CNS tumors, contrasted with adult counterparts, stems from their low prevalence.
Approach:
- Single nuclei RNA sequencing (snRNA-seq) was employed on 35 pediatric CNS tumors and 3 non-tumoral brain tissues, analyzing 84,700 nuclei.
- Characterized tumor heterogeneity and transcriptomic alterations, identifying distinct cell subpopulations within specific tumor types.
- Investigated pathways associated with neural stem cell-like populations, known for therapy resistance.
Key Points:
- Identified cell subpopulations, such as radial glial cells in ependymomas and oligodendrocyte precursor cells in astrocytomas.
- Observed pathways linked to neural stem cell-like populations, potentially contributing to therapeutic resistance.
- Detected transcriptomic alterations specific to pediatric CNS tumor types, distinct from non-tumoral tissues, while controlling for cell type variations.
Conclusions:
- The findings suggest potential tumor type and cell type-specific therapeutic targets for pediatric CNS tumors.
- This research addresses knowledge gaps in single-cell gene expression profiles for understudied pediatric CNS tumor types.
- Enhanced understanding of gene expression profiles in single cells across various pediatric CNS tumors provides a foundation for future treatment strategies.
