Ester Calvo Fernández, Lorenzo Tomassoni, Xu Zhang, Junqiang Wang, Aleksandar Obradovic, Pasquale Laise, Aaron T Griffin, Lukas Vlahos, Hanna E Minns, Diana V Morales, Christian Simmons, Matthew Gallitto, Hong-Jian Wei, Timothy J Martins, Pamela S Becker, John R Crawford, Theophilos Tzaridis, Robert J Wechsler-Reya, James Garvin, Robyn D Gartrell, Luca Szalontay, Stergios Zacharoulis, Cheng-Chia Wu, Zhiguo Zhang, Andrea Califano, Jovana Pavisic
Diffuse Midline Gliomas (DMGs) are universally fatal, primarily pediatric malignancies affecting the midline structures of the central nervous system. Despite decades of clinical trials, treatment remains limited to palliative radiation therapy. A major challenge is the coexistence of molecularly distinct malignant cell states with potentially orthogonal drug sensitivities. To address this challenge, we leveraged established network-based methodologies to elucidate Master Regulator (MR) proteins representing mechanistic, non-oncogene dependencies of seven coexisting subpopulations identified by single-cell analysis-whose enrichment in essential genes was validated by pooled CRISPR/Cas9 screens...
March 17, 2024: bioRxiv