A spatially resolved human glioblastoma atlas reveals distinct cellular and molecular patterns of anatomical niches

Abstract Glioblastoma (GBM) is a highly plastic ecosystem where the complex interplay between different cellular components contributes to disease progression. Although single-cell RNA (scRNA)-seq has revealed remarkable cellular heterogeneity of GBM, our knowledge regarding the spatial organization of its cellular components is currently lacking. Here we created a comprehensive dataset of 115,914 spatial transcriptomes across 32 tissue sections with matched multi-omics profiling on a set of genotyped glioma samples. We present spatial maps of 56 fine-grained cellular components, including previously unrecognized subtypes of oligodendrocytes and stromal cells, and their spatial interaction networks in each GBM- associated anatomical niche. 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.