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

Area of Science:

• Neuro-oncology
• Cancer Biology
• Genomics

Background:

• Glioblastoma (GBM) is a lethal brain tumor with distinct histopathological features: pseudopalisading cells around necrosis (PAN) and microvascular proliferation (MVP).
• The spatial molecular and cellular organization of these GBM hallmarks remains poorly understood.

Purpose of the Study:

• To elucidate the spatial organization of molecular and cellular components within GBM's PAN and MVP regions.
• To identify niche-specific transcriptional programs and characterize cellular differences between PAN and MVP.

Main Methods:

• Utilized bulk RNA sequencing, spatial transcriptomics, and single-cell RNA sequencing (scRNA-seq) on GBM patient data.
• Analyzed spatial domains, identified niche-specific gene signatures, and characterized endothelial cell (EC) phenotypes.
• Performed single-cell trajectory analysis to understand glioblastoma stem cell (GSC) differentiation.

Main Results:

• Discovered spatially distinct domains with niche-specific signatures (NDRG1, EPAS1) in PAN and MVP regions.
• Identified two distinct EC phenotypes enriched in MVP and PAN regions, with PAN-associated ECs showing copy number variations similar to GBM cells.
• Single-cell trajectory analysis indicated GSC differentiation towards ECs.

Conclusions:

• Necrosis cores (PAN) and microvascular proliferation (MVP) are key indicators of aggressive GBM within the tumor microenvironment.
• This research provides novel cellular and molecular insights into glioblastoma progression and tumor heterogeneity.