Single Cell Spatial Profiling of the Matrisome Identifies Region-Specific Adhesion and Signaling Networks in Glioblastoma

Authors

Arpan De
Santiago A Forero
Ali Pirani
John E Morales
Marisol De La Fuente-Granada
Sumod Sebastian
Jason T Huse
Leomar Y Ballester
Jeffrey S Weinberg
Frederick F Lang
Kadir C Akdemir
Joseph H McCarty

Language

English

Publication Date

12-9-2025

Journal

Communications Biology

DOI

10.1038/s42003-025-09270-7

PMID

41366031

PMCID

PMC12769532

PubMedCentral® Posted Date

12-9-2025

PubMedCentral® Full Text Version

Post-print

Abstract

The human brain contains a milieu of extracellular matrix (ECM) components that promote normal development and physiology. ECM signaling pathways are often dysregulated in brain pathologies including the malignant cancer glioblastoma (GBM). Here, we used single-cell spatial transcriptomic platforms to map the expression of nearly 400 ECM genes in matching non-cancerous brain and GBM samples. At least four different GBM cell populations have been identified that show unique ECM expression profiles and spatial enrichment in distinct intratumor regions. Spatial mapping demonstrates largely non-overlapping expression signatures of ECM components in GBM stromal cell types, particularly in vascular endothelial cells and microglia/macrophages. Comparisons of GBM versus lower grade astrocytoma samples identifies differential expression of key ECM components. Computational analysis reveals novel ECM ligand-receptor networks between GBM and stromal cells. This spatial atlas provides new insights into ECM control of brain tumor initiation and progression and identifies potential targets for therapy in GBM.

Keywords

Humans, Glioblastoma, Brain Neoplasms, Signal Transduction, Single-Cell Analysis, Extracellular Matrix, Gene Expression Regulation, Neoplastic, Gene Expression Profiling, Extracellular Matrix Proteins, Cell Adhesion, Transcriptome, Tumor Microenvironment

Published Open-Access

yes

Recommended Citation

De, Arpan; Forero, Santiago A; Pirani, Ali; et al., "Single Cell Spatial Profiling of the Matrisome Identifies Region-Specific Adhesion and Signaling Networks in Glioblastoma" (2025). Faculty, Staff and Student Publications. 5247.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5247