Single cell spatial profiling of the matrisome identifies region-specific adhesion and signaling networks in glioblastoma

The human brain contains a milieu of extracellular matrix (ECM) components that promote normal development and physiology. ECM signaling pathways are often dysregulated in brain pathologies including the malignant cancer glioblastoma (GBM). Here, we used single-cell spatial transcriptomic platforms to map the expression of nearly 400 ECM genes in matching non-cancerous brain and GBM samples. At least four different GBM cell populations have been identified that show unique ECM expression profiles and spatial enrichment in distinct intratumor regions. Spatial mapping demonstrates largely non-overlapping expression signatures of ECM components in GBM stromal cell types, particularly in vascular endothelial cells and microglia/macrophages. Comparisons of GBM versus lower grade astrocytoma samples identifies differential expression of key ECM components. Computational analysis reveals novel ECM ligand-receptor networks between GBM and stromal cells. This spatial atlas provides new insights into ECM control of brain tumor initiation and progression and identifies potential targets for therapy in GBM.