Decoding Heterogeneous and Coordinated Tissue Architecture in Glioblastoma Using Spatial Transcriptomics
Glioblastoma multiforme (GBM) stands as a devastating human malignancy known for its aggressive nature and resistance to multiple therapeutic interventions. Despite extensive intra-tumor heterogeneity unveiled by single-cell transcriptomic studies, the spatial intricacies of this heterogeneity remain largely unknown. This study leveraged clinical GBM specimens to explore gene expression heterogeneity using spatial transcriptomics technology. Our findings unveiled a prominent enrichment of the tissue stem cell signature in the region between necrosis and the peritumoral area, exhibiting a positive correlation with the signature of the mesenchymal subtype. Additionally, the upregulated genes in these regions demonstrated associations with ECM-receptor interaction, Proteoglycans, as well as the VEGF and ANGPT signaling pathways. In contrast, signature genes linked to Glycogen metabolism and Oxidative Phosphorylation were prominently expressed across all samples, irrespective of pathological zoning. Notably, Creatine metabolism showed enrichment in various cell populations except for the vascular-enriched areas. These spatial profiles not only serve as a reference but also provide a profound guide for future functional and mechanistic investigations into the progression of GBM. Overall design: Tumor tissues were procured from patients diagnosed with treatment-naive GBM (WHO Grade IV). For ST sequencing, 16 fresh tissue samples were extracted via surgery from 3 glioblastoma patients.