Elucidating mechanisms of Gliomagenesis: Role of Glioma Stem Cells

High-grade gliomas (HGGs) represent the most frequent primary brain tumor in the adult population and inevitably have a dismal prognosis. Patients suffering from these type of tumor respond only minimally to therapies, including neurosurgery, radiation, first and second line chemotherapy. HGGs are composed of a heterogeneous population of cells that include many with stem-cell-like properties. The acquisition of stem-like traits has been described to contribute to glioma initiation, growth, and escape to therapies. Here we investigated the role of the transcription factor myeloid Elf-1 like factor (MEF, also known as ELF4) in gliomas. We found that MEF is highly expressed in both human and mouse glioblastomas and its absence impairs gliomagenesis in a PDGFdriven glioma mouse model. We show that modulation of MEF levels in both mouse neural stem cells and human glioblastoma cells has a significant impact on neurosphere formation. Moreover, we identify Sox2 as a direct downstream target of MEF. Taken together, our studies implicate MEF as a previously unrecognized gatekeeper gene in gliomagenesis that promotes stem cell characteristics through Sox2 activation.