Multi-transcriptomics reveals niche-specific expression programs and endothelial cells in glioblastoma

• DOI: 10.1186/s12967-025-06185-z
• Publication Date: 2025-04-15T10:59:35Z
• Authors: Jiukun Hu; Xiaohan Sa; Yue Yang; Yuwen Han; Jie Wu; Minxuan Sun; Shaheryar Shafi; Nafees Ahmad; Sami Siraj; Jiao Yang; Yuanshuai Zhou

Glioblastoma (GBM) is a highly lethal malignant intracranial tumor, distinguished from low-grade glioma by histopathological hallmarks such as pseudopalisading cells around necrosis (PAN) and microvascular proliferation (MVP). To date the spatial organization of molecular cellular components these specific features has not been fully elucidated. Here, using bulk RNA sequencing, transcriptomic single cell sequencing (scRNA-seq) data GBM patients, we identified niche-specific transcriptional programs characterized differences in expression between PAN MVP. Notably, discovered spatially distinct domains within tumor core signatures: NDRG1 EPAS1, specifically expressed MVP regions. The clustering results showed two phenotypes endothelial (ECs) were enriched regions, respectively. PAN-associated exhibit copy number variations similar to those cells. Single trajectory analysis reveals pseudotime trajectory, indicating differentiation glioblastoma stem (GSCs) toward ECs. Necrosis cores which are surrounded hypoxic perivascular niches area microenvironment, have considered standardized morphological indicators aggressive GBM. Our findings provide insights into progression.