SOX2 Binds to CD133 in Glioblastoma Stem Cells to Regulate Cellular Stress Pathways Underlying Treatment Resistance

Glioblastoma (GBM) remains a formidable challenge in clinical settings due to limited treatments available for patients. The surface protein CD133 identifies glioblastoma stem cells (GSCs), cells capable of overcoming therapeutic pressures and correlate with more aggressive tumor phenotypes. In our study, we utilized a CRISPR-based genetic screen and Cleavage Under Targets and Release Using Nuclease (CUT&RUN) workflows to distinguish molecular differences between healthy neural stem cells (NSCs) and GSCs. This revealed heightened SOX2 expression directly binds to the PROM1 gene in GSCs, and upregulates genes associated with stress responses including those contributing to chemoradiation resistance. Our findings demonstrate the power of complementary genomic tools, CRISPR screens with CUT&RUN, to unravel complex gene regulatory networks. This integrated approach offers insights into overlapping fields of cancer biology and stem cell research.