36 Isolation of Candidate Glioblastoma-Initiating Cells From Multiple Regions of the Adult Mammalian Brain Using Platelet-Derived Growth Factor C

Brain Cancer Canada Travel Award Recipient An important observation in neurobiology was the discovery of neural stem cells (NSCs) in the adult mammalian brain by Reynolds and Weiss. Although ‘brain repair’ was the initial thrust of research that followed this observation, the enduring contribution may lie in neuro-oncology where dormant stem cells in the adult brain are thought to be the cells-of-origin of GBM. The idea that ‘remnants’ of the developing brain give rise to lethal cancers years later is fascinating but difficult to study without a model system. The current method for culturing NSCs from the stem cell-rich subventricular zone (SVZ) relies on media supplemented with Epidermal Growth Factor and Fibroblast Growth Factor (EGF/FGF). These cells can be maintained indefinitely but are proliferative, unlike how origin-specific stem cells behave. Furthermore, most GBMs arise in normal-appearing brain, not from expanding masses of non-cancerous stem cells. Here, we show that quiescent NSCs can be isolated from the SVZ and cerebral cortex of adult mice using Platelet-Derived Growth Factor C (PDGFC). These SOX2/Nestin positive cells grow in small minimally enlarging spheres and are capable of multi-lineage differentiation, can expand in EGF/FGF, and transition to oligodendrocyte progenitor cells in PGDFC+FGF. Gene expression analysis reveals that NSCs harvested using PDGFC are similar to NSCs in EGF/FGF, but based on an analysis of quiescence genes, are more like SVZ tissue thanNSCs in EGF/FGF. We are testing whether P53 null NSCs isolated in PDGFC then switched to PDGFA become growth factor-independent GBM-like cells (Bohm et al., 2020).