In Situ Single-Cell Spatial Profiling of Matrisome Gene Expression in Glioblastoma

Glioblastoma (GBM) is the most common and aggressive primary brain cancer in adults, characterized by robust infiltrative growth and invasion within the neural microenvironment. While various stromal cells, including astrocytes, microglia, and vascular cells in the microenvironment, communicate with GBM cells to promote growth and invasion, relatively less is known about another critical component of the tumor stroma: the extracellular matrix (ECM). The matrisome comprises hundreds of ECM genes and affiliated adhesion and signaling components; however, little is understood about (i) the repertoire of matrisome genes and proteins expressed in GBM, (ii) the stromal and cancer cells of origin that express different matrisome factors, and (iii) how these components are interconnected to drive tumor malignancy. Here, we have used in situ single-cell transcriptomics to analyze the spatial expression of nearly 350 genes that constitute the human brain matrisome. Our efforts have identified several differentially expressed matrisome genes involved in ECM adhesion and signaling between cancer and stromal cells. Additionally, matrisome genes associated with low-grade glioma pathogenesis and progression to high-grade GBM have been identified and spatially mapped. Collectively, these experiments reveal the single-cell origins of differentially expressed ECM biomarkers as well as their spatial expression patterns in brain tumors. These findings may lead to new therapeutic efforts to inhibit matrisome components to benefit patients with malignant brain cancer.