Seoul National University Brain Tumor Hub

Spatial Resoultion of Genomic Changes in Glioblastoma

Glioblastoma (GBM) is a highly plastic ecosystem where the complex interplay between different cellular components contributes to disease progression. Although single cell RNA-seq greatly helped us to understand cellular heterogeneity of GBM, our knowledge regarding the spatial organization of its cellular components is currently lacking. We performed spatial transcriptomics with matched multiomics profiling on a set of genotyped glioma samples. We present spatial maps of 10 major cellular components and their spatial interaction networks, including previously unrecognized subtypes of oligodendrocyte and stromal cell populations in GBM. This work revealed that each GBM anatomical niche harbors a distinct combination of cellular components. Furthermore, the deconvolution of bulk RNA-seq data using the integrated spatial and single cell atlas revealed clinically relevant GBM ecotypes. Our data provides comprehensive insights into the cellular architecture of GBM at high spatial resolution. It will be a valuable resource to develop effective combinatorial therapies to target all tumor-fostering niches simultaneously.