Multi-Transcriptomic Analysis Reveals GSC-Driven MES-Like Differentiation via EMT in GBM Cell-Cell Communication
Weichi Wu1, Po Zhang2, Dongsheng Li3
1Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
Biomedicines
|June 26, 2025
Summary
Glioma stem cells (GSCs) drive glioblastoma (GBM) progression via epithelial-mesenchymal transition (EMT) signaling. Targeting EMT pathways offers a potential new therapeutic strategy for GBM treatment.
Area of Science:
- Oncology
- Genomics
- Cell Biology
Background:
- Glioblastoma (GBM) is a highly malignant brain tumor driven by glioma stem cells (GSCs).
- Understanding GSC communication is crucial for identifying new therapeutic targets.
- This study investigates GSC communication patterns in GBM using multi-transcriptomic analysis.
Purpose of the Study:
- To analyze intercellular communication networks in GBM.
- To identify biological pathways involved in GSC communication.
- To explore the role of epithelial-mesenchymal transition (EMT) in GSC function and GBM progression.
Main Methods:
- Utilized CellChat for quantitative inference of intercellular communication networks from scRNA-seq data.
- Performed gene set enrichment analysis (GSEA) to identify EMT pathways.
- Employed spatial transcriptomics and single-sample GSEA (ssGSEA) to link EMT with GSC states and proliferation.
Main Results:
- GSC communication patterns are strongly associated with EMT.
- High expression of EMT-related genes in GBM, particularly in GSCs, correlates with poor prognosis.
- EMT signatures are most enriched in mesenchymal-like (MES-like) GSCs, which are linked to the most unfavorable outcomes.
Conclusions:
- GSCs promote GBM progression through EMT-patterned intercellular communication.
- EMT-associated genes may drive GSC differentiation towards a poor-prognosis MES-like phenotype.
- Targeting EMT pathways presents a potential novel therapeutic strategy for GBM.
