Stem cell morphology defines functional heterogeneity and therapeutic vulnerabilities in glioblastoma
Barelli C., Bonfanti M., Mirabella F., Ricca D., Alizadehmohajer N., Bosotti R., Bertani I., Sokolova V., Campione A., Sicuri G.M., Peano C., Faletti S., Stefini R. and Kalebic N.
Here we link glioblastoma stem cell morphology with clinically relevant functions. We developed CellShape-seq which integrates cell morphology with transcriptomics, revealing three distinct morphoclasses of glioblastoma stem cell linked to invasion, intercellular networking and therapy response. We further show that chemoresistance has morphotype-specific vulnerabilities. Targeting these morphoclass-specific mechanisms sensitizes resistant GSCs to temozolomide, supporting morphology-informed therapeutic strategies for GBM.
DOI: 10.1093/neuonc/noag235The PRECISE European initiative for cancer-vulnerability mapping and prediction
Francesco Iorio, Mathew J. Garnett, Pedro Beltrao, Maximilian Billmann, Larissa Bless, Christoph Bock, Michael Boutros, Alejandra Bruna, Piero Carninci, Giovanni Ciriello, Isidro Cortés-Ciriano, Giuseppina D’Alessandro, Roberta Esposito, Stefania Faletti, Emanuel Gonçalves, Syed Haider, Nereo Kalebic, Manuel Kaulich, Giuseppe Leuzzi, Nuria Lopez-Bigas, Christopher J. Lord, Evangelia Petsalaki, Stephen Pettitt, Ludovica Proietti, Roland Rad, Nevenka Radic, Colm J. Ryan, Jonathan L. Schmid-Burgk, Sumana Sharma, Andrea Sottoriva, Christopher Tape, Livio Trusolino, Jolanda van Leeuwen, David Walter, Lodewyk Wessels & the PRECISE consortium
Together with 30 other research groups, the Kalebic Lab is part of PRECISE (Predictive Relationships Explaining Cancer Genetic Interactions and Synthetic Essentiality), a pan-European network coordinated by Francesco Iorio from Human Technopole, that aims to combine high-throughput perturbation biology, multimodal profiling and AI-driven inference to predict cancer vulnerabilities in disease-relevant models. The vision and the mission of PRECISE have now been presented in a Nature Genetics commentary.
DOI: 10.1038/s41588-026-02658-z