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Nuclei Isolation from Fresh Frozen Brain Tumors for Single-Nucleus RNA-seq and ATAC-seq
Published on: August 25, 2020
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Inferred developmental origins of brain tumors from single-cell RNA-sequencing data
Su Wang1, Rachel Naomi Curry2,3, Malcolm F McDonald4,5,2
1Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA.
Neuro-Oncology Advances
|May 5, 2025
Summary
A new computational tool, COORS, identifies developmental origins of brain tumors by analyzing single-cell RNA sequencing data. This tool aids in understanding tumor heterogeneity and developing targeted therapies for brain cancers.
Area of Science:
- Neuroscience
- Oncology
- Computational Biology
Background:
- Reactivation of neurodevelopmental programs is observed in cancer, suggesting shared biological processes between development and brain tumors.
- Understanding dysregulated developmental factors in brain tumor progression is crucial for identifying therapeutic targets.
- Single-cell RNA sequencing (scRNA-Seq) enables high-resolution analysis of developmental program dysregulation in brain tumors.
Purpose of the Study:
- To identify the developmental origins of brain tumors using scRNA-Seq data.
- To develop a computational tool for annotating developmental-like cell states in brain tumors.
Main Methods:
- Introduction of COORS (Cell Of ORigin like CellS), a computational tool trained on human brain developmental scRNA-Seq datasets.
- COORS utilizes cell type-specific multilayer perceptron models and a developmental cell type tree to model cell type probabilities.
- Application of COORS to medulloblastoma (MB), glioma, and diffuse midline glioma (DMG) datasets.
Main Results:
- COORS identified developmental-like cells representing putative cells of origin in MB, glioma, and DMG.
- The tool provides cell of origin classification and cell age regression, revealing developmental insights into tumor subgroups.
- Specific findings include identification of outer radial glia in IDHWT glioma and oligodendrocyte precursor cells (OPCs) and neuronal-like cells in IDHMUT glioma, with OPCs showing bimodal developmental timing.
Conclusions:
- The study enhances understanding of brain tumor heterogeneity by pinpointing developmental origins.
- COORS provides novel markers associated with developmental states in brain tumors.
- This research contributes to paving the way for tailored therapeutic strategies in brain oncology.
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