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Related Experiment Video

Updated: Apr 25, 2026

Nuclei Isolation from Fresh Frozen Brain Tumors for Single-Nucleus RNA-seq and ATAC-seq

Nuclei Isolation from Fresh Frozen Brain Tumors for Single-Nucleus RNA-seq and ATAC-seq

Published on: August 25, 2020

Mapping glioblastoma's isoform diversity using long-read single-cell analysis.

Wenshu Tang¹, Cario W S Lo¹, Annie T W Chu¹

¹Hong Kong Genome Institute, Hong Kong SAR, China.

Nature Communications

|April 23, 2026

Summary

This summary is machine-generated.

This study uses single-cell long-read RNA sequencing to map glioblastoma (GBM) cell diversity at the isoform level. Researchers discovered novel tumor-specific RNA variants with potential as neoantigens for cancer immunotherapy.

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Last Updated: Apr 25, 2026

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Laser Capture Microdissection of Glioma Subregions for Spatial and Molecular Characterization of Intratumoral Heterogeneity, Oncostreams, and Invasion

Laser Capture Microdissection of Glioma Subregions for Spatial and Molecular Characterization of Intratumoral Heterogeneity, Oncostreams, and Invasion

Published on: April 12, 2020

Area of Science:

Genomics
Oncology
Molecular Biology

Background:

Glioblastoma (GBM) is an aggressive brain tumor characterized by significant intratumoral heterogeneity and dysregulated RNA splicing.
Alternative splicing significantly impacts cellular identity, function, tumor progression, and treatment resistance in GBM.
Existing short-read sequencing methods limit the comprehensive analysis of full-length RNA isoforms in GBM.

Purpose of the Study:

To create an isoform-level atlas of glioblastoma using single-cell long-read RNA sequencing.
To identify novel, tumor-specific RNA isoforms and potential therapeutic targets within glioblastoma.
To explore the potential of newly discovered isoforms as neoantigens for cancer immunotherapy.

Main Methods:

Application of single-cell long-read RNA sequencing to capture full-length transcripts in glioblastoma cells.
Development of a framework to identify and prioritize tumor-restricted isoforms.
Analysis of differential transcript usage across distinct glioblastoma cell populations.
Prediction of peptide binding to MHC class I molecules for neoantigen identification.

Main Results:

Hundreds of isoforms with differential transcript usage were identified across diverse glioblastoma cell populations.
A framework successfully prioritized tumor-restricted isoforms, identifying potential surface-intracellular target pairs in seven patients.
6,524 novel isoforms were discovered, including 179 that are specific to glioblastoma.
Peptides derived from tumor-specific isoforms demonstrated strong predicted binding to MHC class I molecules.

Conclusions:

Single-cell long-read RNA sequencing provides unprecedented resolution for characterizing glioblastoma isoform complexity.
The identified tumor-specific isoforms and target pairs offer potential avenues for developing novel dual-specific ligand-based therapies.
Newly discovered tumor-specific isoforms represent a promising source of potential neoantigens for glioblastoma immunotherapy.