CNSC-73. CHARACTERIZING THE INTERACTIONS BETWEEN PRIMARY GLIOBLASTOMA AND OLIGODENDROCYTE PROGENITOR CELLS

Abstract Resection of glioblastoma (GBM) often only includes the gadolidium contrast-enhancing (CE) solid portion of the tumor and radiation therapy also targets this region. These therapies leave behind infiltrating tumor cells that lay beyond the CE in the non-enhancing region (NE) with the capacity to propagate the tumor following therapy. Non-transformed cell types in the brain have been shown to promote GBM progression via a variety of mechanisms. We performed single nucleus RNA-sequencing (snRNA-seq) on 17 biopsies from the NE and CE regions of seven different primary IDH WT glioblastoma tumors during maximal resection surgery. While some OPCs are present in the NE region, they are almost absent in the CE region, a finding corroborated by our prior study of recurrent tumors. OPCs, share many genes with GBM and also cycle. Prior work has demonstrated that in the developing and adult brain young, more fit OPCs can outcompete older OPCs leading us to hypothesize that brain tumor cells can compete with non-transformed OPCs. To explore possible interactions between GBM and OPCs we utilized a predictive cell-cell interaction software finding that OPCs express transcripts that are predicted to respond to GBM signals to induce proliferation, migration and differentiation. Compared to snRNA-seq of healthy OPCs, the OPCs from our biopsies were more likely to be proliferative, migratory, and differentiated. To assess possible enrichment of pathways associated with a more competitive state, we performed differential expression between OPCs contained in our biopsies and GBM cells. This revealed a significant enrichment of the YAP1 pathway which is associated with a more competitive state. GBM cells were predicted to be activated by OPCs to proliferate, migrate and have increase synaptic activity. We are testing these hypotheses, using in-vitro and in-vivo assays.