High-grade gliomas are aggressive and uniformly fatal tumors,composed of a heterogeneous population of cells that include many with stem-cell-like properties.The acquisition of stem-like traits might contribute to glioma initiation,growth,and recurrence.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 PDGF-driven 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. High-grade gliomas are aggressive and uniformly fatal tumors, composed of a heterogeneous population of cells that include many with stem-cell-like properties. The acquisition of stem-like traits might contribute to glioma initiation, growth, and recurrence. Here we 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 PDGF-driven 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.