Single-Cell Transcriptomics Uncover IBSP as a Mediator of Tumor-Associated Microglia and Macrophages-Driven Glioblastoma Progression
Year: 2025
Type: preprint
Abstract: 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.
Source: Research Square
Authors: Atul Anand, Rikke Frydendahl Sick Olsen, Dylan Harwood, Mark Burton, Anne Grangaard, Jérémy Ariey-Bonnet, Philip Ahle Erichsen, Vilde Pedersen, Julie Jacobsen, Maria Brown, Nicolai Bager, Jesper Ewald, Signe Michaelsen, Maja Dembic, Lihong Xu, Sara Artzi, Juyeun Lee, Krister Wennerberg, Justin Lathia, Torben Kruse, Frantz Poulsen, Bo Halle, Christian Pedersen, Jane Skjoeth-Rasmussen, Mads Thomassen, Bjarne Kristensen
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4411346660