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Harmonized single-cell landscape, intercellular crosstalk and tumor architecture of glioblastoma

ABSTRACT: Harmonized single-cell landscape, intercellular crosstalk and tumor architecture of glioblastoma

PROVIDER: PRJNA870065 | ENA |

REPOSITORIES: ENA

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Harmonized single-cell landscape, intercellular crosstalk and tumor architecture of glioblastoma

Project description:Glioblastoma, IDH wt (GB) is an aggressive brain malignancy associated with a dismal prognosis and poor quality of life. Large-scale data integration can help to uncover unexplored tumor pathobiology. To resolve the composition of the tumor milieu and recreate the cellular map of GB, we created the ‘GBmap’, a curated resource that at its core harmonizes 16 datasets gathering 110 patients and spanning over 330 thousand cells. By transfer learning, we ‘upgraded’ our atlas reference (extended GBmap) with another ten datasets, including our own profiled GB tissues resulting in a collection of 26 studies, 240 patients, and more than 1,1 million cells. We showcase the applications of our resource in several scenarios, from reference mapping to biological discoveries. The GBmap represents a framework that allows the streamlined characterization, integration, and interpretation of new data and provides a platform for exploratory analysis, hypothesis generation, and testing.

2025-05-09 | GSE211376 | GEO

Glioblastoma-cortical organoids recapitulate cell state heterogeneity and intercellular transfer

Project description:Glioblastoma is characterized by heterogeneous malignant cells that are functionally integrated within the neuroglial microenvironment. Here, we model this ecosystem by growing glioblastoma into long-term cultured human cortical organoids that contain the major neuroglial cell types found in the cerebral cortex. Single-cell RNA-seq analysis suggests that, compared to matched gliomasphere models, glioblastoma cortical organoids (GCO) more faithfully recapitulate the diversity and expression programs of malignant cell states found in patient tumors. Additionally, we observe widespread transfer of glioblastoma transcripts and GFP proteins to non-malignant cells in the organoids. Mechanistically, this transfer involves extracellular vesicles and is biased towards defined glioblastoma cell states and astroglia cell types. These results extend previous glioblastoma-organoid modeling efforts and suggest widespread intercellular transfer in the glioblastoma neuroglial microenvironment.

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Landscape of intercellular crosstalk in fatty liver disease revealed by single-cell secretome analysis

Project description:Landscape of intercellular crosstalk in fatty liver disease revealed by single-cell secretome analysis

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Landscape of intercellular crosstalk in fatty liver disease revealed by single-cell secretome analysis

Project description:Cell-cell communications via ligand-receptor signaling are a fundamental feature of complex organs. In addition to hepatocytes, the mammalian liver harbors several distinct cell types, including endothelial cells, hepatic stellate cells (HSC), cholangiocytes, the resident macrophage Kupffer cells, and other immune cells, collectively known as non-parenchymal cells (NPC) 1-5. Paracrine signaling among NPC is important for tissue homeostasis and has been implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH), an emerging epidemic linked to metabolic syndrome 6-8. Despite this, the global landscape of intercellular signaling in the liver has not been comprehensively elucidated. Here we perform single-cell RNA sequencing and secretome analysis on liver NPC isolated from healthy and diet-induced NASH mice. Our analysis revealed highly specific patterns of the cellular sources of secreted ligands and membrane receptors and a network of paracrine and autocrine signaling at the single-cell level. Comparative analysis of secretome gene expression uncovered a global disruption of the liver endothelial signaling network during NASH pathogenesis. The HSC secretome encompasses extracellular matrix proteins, signaling ligands (stellakines) and three distinct functional classes of membrane receptors. Liver macrophage undergoes a marked expansion in NASH with the emergence of a new population marked by expression of Triggering receptor expressed on myeloid cells 2 (Trem2) and activation of a transcriptional program underlying phagocytosis, lysosomal degradation and antigen presentation. These results provide a high-resolution blueprint of intercellular crosstalk in mammalian liver and illustrate the complexity and richness of cell-cell signaling in liver physiology and disease.

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Glioblastoma-cortical organoids recapitulate cell state heterogeneity and intercellular transfer

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Crosstalk with astrocytes establishes tumor edge in glioblastoma

Project description:Crosstalk with astrocytes establishes tumor edge in glioblastoma

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The Multi-Layered Transcriptional Architecture of Glioblastoma Ecosystems [10X]

Project description:The Multi-Layered Transcriptional Architecture of Glioblastoma Ecosystems [10X]

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The Multi-Layered Transcriptional Architecture of Glioblastoma Ecosystems [smart-seq2]

Project description:The Multi-Layered Transcriptional Architecture of Glioblastoma Ecosystems [smart-seq2]

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Decoding Heterogeneous and Coordinated Tissue Architecture in Glioblastoma Using Spatial Transcriptomics

Project description:Decoding Heterogeneous and Coordinated Tissue Architecture in Glioblastoma Using Spatial Transcriptomics

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