Cell of Origin and Cancer Stern Cells in Tumor Suppressor Mouse Models of Glioblastoma

The cellular origins and the mechanisms of progression, maintenance of tumorigenicity, and therapeutic resistance are central questions in the glioblastoma multiforme GEM) field. Using tumor suppressor mouse models, our group recently reported two independent populations of adult OHM-initiating central nervous system progenitors. We found different functional and molecular subtypes depending on the tumor-initiating cell lineage, indicating that the cell of origin is a driver of OHM subtype diversity. Using an in vivo model, we also showed that GEM cancer stem cells (CSCs) or glioma stem cells (GSCs) contribute to resistance to chemotherapeutic agents and that genetic ablation of GSCs leads to a delay in tumor progression. These studies are consistent with the cell of origin and CSCs as critical regulators of the pathogenesis of GEM.