TMIC-33. Single Cell Spatial Profiling of Matrisome Gene Expression in Glioblastoma

The human brain contains a rich milieu of extracellular matrix (ECM) components that promote normal physiology and are often dysregulated in pathologies including the malignant cancer glioblastoma (GBM). We have used in situ single-cell spatial transcriptomic platforms to map the expression patterns of nearly 400 ECM-related genes in multiple GBM samples (IDH1 wild type). Our analysis identifies at least four different GBM cell populations with unique ECM expression profiles that show spatial enrichment in distinct intratumor regions. Spatial mapping also demonstrates largely non-overlapping expression signatures of various ECM components in stromal cell types, particularly in GBM vascular endothelial cells and reactive microglia/macrophages. Comparisons of GBM versus lower-grade II and III astrocytoma samples (IDH1 R132H) identifies differential expression of key ECM components, including elevated levels of select ECM glycoproteins (IGFBP2 and MGP) and ECM-affiliated proteins (ANXA1 and ANXA2). In addition, we detect spatially enriched expression of COL8A1 (collagen), LUM (proteoglycan), and POSTN (ECM glycoprotein) in perivascular stromal cells in GBM but not in lower grade tumors. Computational analysis of putative ligand-receptor interactions reveals novel communication networks between cancer cells and stromal components, particularly in regions of GBM microvascular proliferation and pseudopalisading necrosis. In summary, this comprehensive spatial map provides new insights into ECM control of tumor initiation and progression and identifies potential therapeutic targets within the GBM microenvironment.