Single-Cell Transcriptomics Uncover IBSP as a Mediator of Tumor-Associated Microglia and Macrophages-Driven Glioblastoma Progression

Tumor-associated microglia and macrophages (TAMs) represent the second largest cellular population in glioblastoma and play a pivotal role in tumor progression. However, the transcriptional landscape underlying CD11b ⁺ TAM heterogeneity remains poorly characterized. Here, we employ single-cell RNA sequencing to dissect and compare the heterogeneity of CD11b ⁺ TAMs in glioblastoma versus non-tumor control tissue, identifying a distinct subpopulation expressing integrin-binding sialoprotein (IBSP). Spatial analyses using GeoMx and immunofluorescence staining reveal that IBSP expression is predominantly localized to TAMs residing in perivascular niches and pseudo-palisades. Functionally, we show that glioblastoma-derived TAMs secrete IBSP, which enhances self-renewal in patient-derived glioblastoma models. Transcriptomic profiling of IBSP-stimulated glioblastoma cells demonstrates upregulation of Inhibitor of DNA Binding ( ID ) genes, suggesting that IBSP promotes tumor aggressiveness by activating pro-tumorigenic pathways. These findings identify IBSP-positive TAMs as a novel subpopulation with critical roles in shaping the glioblastoma microenvironment and position IBSP as a promising therapeutic target for disrupting tumor-supportive niches in glioblastoma.