The mesenchymal state drives stemness and limits differentiation in glioblastoma
Presenter: Emanuele Filiberto Rosatti, BS;MS Session: Metabolic and Transcriptional Control of Cancer Stem Cell Plasticity Time: 4/20/2026 9:00:00 AM → 4/20/2026 12:00:00 PM
Authors
Emanuele Filiberto Rosatti , Denise Sighel , Anna Veronese , Toma Tebaldi , Alessandro Quattrone Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy
Abstract
Glioblastoma is a highly heterogeneous and lethal brain cancer with limited therapeutic options. Recent single-cell omics studies have emphasized the importance of the proneural-mesenchymal axis and strengthened the link between glioblastoma and neurodevelopment, yet the identity and regulatory drivers of glioblastoma stem cells remain poorly defined. In this work, we combined published single-cell datasets with in vitro models to investigate glioblastoma stemness and the tumor’s response to differentiation cues. Through integrative analysis of single-cell RNA sequencing and single-nucleus ATAC sequencing, we refined the landscape of glioblastoma cellular states. Comparison with human subventricular zone profiles reveals a striking similarity between a mesenchymal-like subpopulation and adult radial glia. We further established a comprehensive differentiation assay incorporating phenotypic, transcriptomic, and proteomic readouts. Using this system, we show that glioblastoma cells exhibit heterogeneous responses to differentiation signals and that mesenchymal-like cells, in particular, display pronounced resistance to lineage commitment. Together, these findings highlight the mesenchymal state as a key barrier to differentiation in glioblastoma and lay the groundwork for targeting its underlying drivers to restore differentiation capacity and potentially improve therapeutic outcomes.
Disclosure
E. Rosatti, None.. D. Sighel, None.. A. Veronese, None.. T. Tebaldi, None.. A. Quattrone, None.
Cited in
Control: 4908 · Presentation Id: 698 · Meeting 21436