The ssDNA binding protein FUBP1 was originally characterised as a transcriptional activator of the MYC oncogene. Surprisingly, however, FUBP1 loss-of-function has been identified as a frequent driver mutation in oligodendroglioma. To understand the networks associated with the unexpected tumour suppressive role for FUBP1 in the brain, we have taken advantage of the conservation of FUBP1 (Psi) in Drosophila. A major impediment to improved glioma treatment is our lack of understanding of the interaction between glioma stem cells and their glial microenvironment. Thus, we aim to elucidate FUBP1/Psi function not only in neural stem cells but also in the cortical glial microenvironment, or niche, providing the structural support and secreted signals required for stemness and differentiation. Our preliminary data demonstrate the importance of FUBP1/Psi in the microenvironment, where specific depletion of Psi in the cortical glia non-autonomously drives neural stem cell expansion. To better understand how FUBP1/Psi non-autonomously controls neural stem cell fate we used Targeted DamID (TaDa) to identify direct, genome-wide, targets in the cortical glia. Intriguingly, targets included secreted proteins predicted to signal from the cortical glia to control fate of neighbouring neural stem cells. Furthermore, analysis of TCGA datasets revealed 82% of the human orthologues of FUBP1/Psi targets are frequently dysregulated in low grade glioma. Together, our data demonstrate Psi normally acts extrinsically in the glial microenvironment to prevent neural stem cell expansion. We therefore hypothesise that FUBP1 loss-of-function in glioma drives stem cell expansion and tumourigenesis, at least in part, by indirectly disrupting the glial microenvironment.