Abstract 6779: Spatial and single-nucleus transcriptomics of human glioblastoma

Abstract

Abstract Glioblastoma (GBM) multiforme is the most aggressive type of brain cancer. These lethal brain tumors are characterized by the inter- and intra-tumor molecular heterogeneity and diverse cell plasticity. We sought to interrogate the immune landscape of GBM, tease out the distinct biological and therapeutic niches in GBM and to understand how the tumor microenvironments mediated the heterogeneity of GBM. We have collected six human GBM samples for spatial profiling and single-nucleus RNA sequencing. Multiple sets of spatial gene panels were designed to capture the cell identities (cancer stem cells, astrocytes, oligodendrocytes, microglia, macrophages, endothelial cells, etc.) and the spatially-resolved expression patterns of genes indicative of different functional states. We also aim to find altered neurovascular units by examining the spatial correlation between cells that highly express angiogenesis markers such as VEGFA with tumor-associated macrophages, which could be recruited to the angiogenic niche by GBM tumor cells. From the spatial RNA dataset of the first two samples, we observed close proximity of tumor-associated macrophages and endothelial cells that form the microvasculature. Our preliminary results from the single-nucleus RNA sequencing and spatial transcriptomics of two samples shed light on the complex cell landscape and the dynamic interaction between tumor cells and infiltrating or resident immune cells in the GBM tumor tissue. Citation Format: Yue Hao, Angela Baker, Brian Hilbush, Marcos Otero, Chris Streck, Karen L. Fink, George J. Snipes, Bruce E. Mickey, Michael Berens. Spatial and single-nucleus transcriptomics of human glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6779.