Project description:To comprehensively define the cellular heterogeneity of glioblastoma (GBM), the GBM CARE (Cellular Analysis of Resistance and Evolution) consortium set out to profile 121 GBMs with extensive clinical annotation, by single-nucleus RNA-sequencing and bulk tumor DNA sequencing. The resulting dataset enabled us to characterize GBM heterogeneity at three levels. First, GBMs are classified by their cellular composition, encompassing malignant, immune, neuronal and glial cell types. Second, within each cell type, and particularly among the malignant cells, we describe the diversity of cellular states and their pathway-based functional activities. Third, after controlling for the frequencies of cellular states, we find that the remaining variation between GBMs highlights three baseline gene expression programs which we labeled Neuronal, Glial, and Extracellular Matrix. These three layers of heterogeneity are inter-related and partially associated with specific genetic aberrations, thereby defining three stereotypic ecosystems in GBM. This work provides an unparalleled view of the multi-layered transcriptional architecture of GBM.
Project description:To comprehensively define the cellular heterogeneity of glioblastoma (GBM), the GBM CARE (Cellular Analysis of Resistance and Evolution) consortium set out to profile 121 GBMs with extensive clinical annotation, by single-nucleus RNA-sequencing and bulk tumor DNA sequencing. The resulting dataset enabled us to characterize GBM heterogeneity at three levels. First, GBMs are classified by their cellular composition, encompassing malignant, immune, neuronal and glial cell types. Second, within each cell type, and particularly among the malignant cells, we describe the diversity of cellular states and their pathway-based functional activities. Third, after controlling for the frequencies of cellular states, we find that the remaining variation between GBMs highlights three baseline gene expression programs which we labeled Neuronal, Glial, and Extracellular Matrix. These three layers of heterogeneity are inter-related and partially associated with specific genetic aberrations, thereby defining three stereotypic ecosystems in GBM. This work provides an unparalleled view of the multi-layered transcriptional architecture of GBM.
Project description:One healthy mouse brain and one glioblastoma tumor derived in the RCAS/Nestin-Tv-a mouse model were processed using the 10x Genomics Visium HD Spatial Gene Expression chemistry.
Project description:Two primary and two post-radiotherapy recurrent glioblastoma tumors derived in the RCAS/Nestin-Tv-a mouse model were processed using the 10x Genomics Visium Spatial Gene Expression v1 chemistry.
Project description:Glioma contains malignant cells in diverse states. Here, we combine spatial transcriptomics with novel computational approaches to uncover the organization of glioma cellular states. We find three prominent modes of organization. First, cells in any given state tend to be spatially clustered, with local environments that are each enriched with one major cellular state. Second, specific pairs of states preferentially reside in proximity across multiple scales. Third, the pairwise interactions that we detect collectively define a global architecture composed of five layers. Hypoxia appears to drive this 5-layered organization, as it is associated with a long-range organization that extends from the hypoxic core to the infiltrative edge of the tumor. Accordingly, tumor regions distant from any hypoxic foci are less organized. In summary, we provide a conceptual framework for the organization of gliomas and highlight the role of hypoxia as a potential long-range tissue organizer.
Project description:Cancer cells display heterogeneous and dynamic states in glioblastoma, but how these malignant states arise and whether they follow a tractable cellular trajectory across tumours is poorly understood. Here, we generate a deep single cell and spatial multi-region atlas of 12 isocitrate dehydrogenase wild-type (IDH-wt) primary glioblastomas that integrates transcriptomic, epigenomic and genomic analysis to comprehensively characterise their tumour heterogeneity. This submission contains the Space Ranger processed outputs from Visium spatial transcriptomic sequencing (10x Genomics), including paired high-resolution H&E tissue images. We also provide an integrated single cell and spatial dataset across 97 Visium sections, including gene expression, cell state abundances, and histopathological annotations.
Project description:Cancer cells display heterogeneous and dynamic states in glioblastoma, but how these malignant states arise and whether they follow a tractable cellular trajectory across tumours is poorly understood. Here, we generate a deep single cell and spatial multi-region atlas of 12 isocitrate dehydrogenase wild-type (IDH-wt) primary glioblastomas that integrates transcriptomic, epigenomic and genomic analysis to comprehensively characterise their tumour heterogeneity. This submission contains the Cell Ranger ARC processed outputs from single nuclei joint transcriptome- and chromatin accessibility-sequencing (10x Genomics). We also provide an integrated single nuclei transcriptomics dataset, comprised of malignant and tumour microenvironment cell type annotations.