BIOS-02. RECAPITULATE TUMOR DIVERSION AND SPATIAL PATTERNING IN GLIOBLASTOMA BACKGROUND

Intra-tumoral heterogeneity of glioblastoma multiforme (GBM) drives aggressive behavior and intrinsic therapeutic resistance. To investigate heterogeneity, high-resolution sequencing techniques provided us to feature tumor molecular subtyping and simulate differentiation. In our study, we proposed to dissect tumor heterogeneity in different anatomical regions by single cell transcriptome analysis. Material and Method We performed single-cell RNA sequencing on 10675 adult IDH-wild type GBM cells from six pairs of tumor core (central necrotic part of tumor) and tumor margin (junction between tumor and brain). Subtyping following RNA velocity was performed to investigate tumor diversity. Result Four subgroups of tumor cells (OPC-like (oligoprogenitor cell), NPC-like (neuroprogenitor cell), AC-like (astrocyte), and MES-like (mesenchymal) )were identified. The higher cell population of OPC/NPC at tumor margin and AC/MES at tumor core was found. The RNA velocity analysis showed the major diversity order was OPC at margin, OPC at core, NPC at margin, and AC with MES at core.

We explore the spatial pattern of tumorigenesis of GBM that OPC at margin part could be the tumor initiating cell. Further investigation of biological characteristics of OPC could be the strategies to block tumor differentiation and progression.