ArticleGenome biology2025
A single-cell atlas of RNA alternative splicing in the glioma-immune ecosystem.
Article in Genome biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- ARGLU1 in Glioma: A Novel Potential Regulator of Splicing, DNA Repair, and Therapeutic Resistance.Cells · 2026Review
- Stepwise Protocol for Alternative Splicing Analysis in Single-Cell SMART-Seq2 RNA-Seq Data.Bio-protocol · 2026Article
- Tracing the genetic legacy of Altaic-speaking populations suggested long-distance migration and multi-source admixture shape the genomic diversity of Xibe and Daur.Human genetics · 2026Article
- Prognostic alternative splicing signatures in esophageal cancer reveal SF3A3 as a key oncogenic splicing factor.Translational cancer research · 2026Article
- Mapping isoforms and regulatory mechanisms from spatial transcriptomics data with SPLISOSM.Nature biotechnology · 2026Article
- A single-cell atlas of RNA alternative splicing in the glioma-immune ecosystem.Genome biology · 2025Article
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10 authors.
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Abstract
backgroundSingle-cell analysis has refined our understanding of cellular heterogeneity in glioma, yet RNA alternative splicing, a critical layer of transcriptome regulation, remains underexplored at single-cell resolution. Here, we present a pan-glioma single-cell alternative splicing analysis in both tumor and immune cells through integrating seven SMART-seq2 datasets of human gliomas to uncover overlooked isoform-level regulations shaping glioma progression and immune responses.
resultsOur analysis reveals lineage-specific alternative splicing regulation among glioma cellular states, with the most divergent alternative splicing landscapes observed between mesenchymal and neuronal-like glioma cells. Notably, this includes events in TCF12 exon 15 and PTBP2 exon 10, two key regulators of mesenchymal and neuronal transcriptomes. Inducing TCF12 exon 15 inclusion in glioma cells with a dCasRx-RBM25 system promotes neuronal gene expression, suppresses genes related to extracellular matrix organization, and enhances sensitivity to radiotherapy. Comparison of core and peripheral glioma cells highlights alternative splicing redox co-regulation of TPM1 and ACTN4, key genes involved in cytoskeletal organization. Further analysis of glioma-infiltrating immune cells reveals altered first exon usage of UGP2 in regulatory T cells and an association between MS4A7 alternative splicing in macrophages and clinical response to anti-PD-1 therapy.
conclusionsThis study emphasizes the role of alternative splicing in glioma cellular heterogeneity, highlighting the importance of an isoform-centric approach to better understand the complex biological processes driving tumorigenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.