Single cell analysis reveals integrin binding sialoprotein-expressing tumor-associated microglia and macrophages in human glioblastoma

ABSTRACT: Tumor-associated microglia and macrophages (TAMs) are critical players in the glioblastoma microenvironment, playing significant roles in tumor progression. A deeper understanding of different TAM subsets is essential for advancing glioblastoma therapy. Here, we dissect the TAMs using single-cell RNA-sequencing, and discover a subpopulation expressing integrin binding sialoprotein (IBSP). RNAscope and immunofluorescence stainings reveal that IBSP expression predominantly is localized to TAMs and vascular structures, with IBSP-expressing TAMs concentrated in the perivascular niche. Functionally we demonstrate that IBSP is secreted by TAMs and promotes the formation of larger and more numerous spheroids in patient-derived glioblastoma models in vitro. Transcriptomic profiling of IBSP-stimulated glioblastoma spheroids reveals upregulation of inhibitor of differentiation (ID) genes, suggesting a mechanism by which IBSP enhances tumor aggressiveness via increased angiogenesis and maintenance of glioma-initiating cells in the perivascular niche. Our findings identify IBSP-positive TAMs as a distinct subpopulation with a critical role in shaping the glioblastoma microenvironment, and highlight IBSP as an attractive therapeutic target for disrupting tumor-supportive niches in glioblastoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE276712 | GEO | 2026/06/30

REPOSITORIES: GEO