COMP-06. GLIOBLASTOMA DEVELOPMENT MIRRORS THE DEVELOPING BRAIN. (5th November 2018) - Couturier, Charles
Abstract: Intratumoral and interpatient heterogeneity are characteristics of glioblastoma and constitute important challenges in overcoming treatment resistance and developing new, more effective therapies. Using single-cell RNA sequencing, we characterized 60 933 cells from 4 developing fetal brains and 8 glioblastomas. By using fetal brain development as a road map, we show a tri-lineage (astrocytic, oligodendrocytic, and neuronal) hierarchical organization in all glioblastomas. In each patient, a population of progenitor cancer cells was found at the apex of this hierarchy. These cells were enriched in our patient-derived glioma stem cell samples, and, like progenitors in the developing brain, were the main dividing cell population within the cancer. Using expression signatures obtained from single-cell RNA-sequencing, we isolated progenitor cancer cells and compared them to other glioblastoma cell types. We showed the progenitors are the most resistant to chemotherapy and the most tumorigenic in mouse xenograft models. This newly found conserved developmental organization points to the cell of origin and suggests new therapeutic approaches.