Spatial and single-cell characterization of human glioblastoma tumor microenvironment reveals malignant cellular communities.

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Title: Spatial and single-cell characterization of human glioblastoma tumor microenvironment reveals malignant cellular communities.
Authors: Lin, Jun (AUTHOR), Chen, Chunpeng (AUTHOR), Li, Shouzhen (AUTHOR), Chen, Liu (AUTHOR), Fang, Minghao (AUTHOR), Fu, Shuqi (AUTHOR), Chen, Kaixing (AUTHOR), Xu, Hao (AUTHOR), Zhang, Fenghuan (AUTHOR), Wang, Rirui (AUTHOR), Jiang, Chen (AUTHOR), Tang, Meifang (AUTHOR), Liu, Zitian (AUTHOR), Wang, Shuyan (AUTHOR), Liu, Ke (AUTHOR), Niu, Chaoshi (AUTHOR), Li, Bin (AUTHOR), Liu, Xu (AUTHOR), Cheng, Chuandong (AUTHOR), Tang, Ai-Hui (AUTHOR)
Source: Nature Neuroscience. Jun2026, Vol. 29 Issue 6, p1342-1354. 13p.
Abstract: Understanding the complex cellular and spatial organization of glioblastoma (GBM) and its microenvironment is crucial for improving diagnosis and treatment. Here we integrated 121 spatial transcriptomics, single-cell RNA sequencing, single-cell assay for transposase-accessible chromatin using sequencing and patch sequencing profiles from 100 patients to characterize primary GBM tissue. We identified four malignant cellular communities that exhibited consistent patterns of cell-type compositions, gene expression and intercellular interactions across patients. We identified two subpopulations of mesenchymal-like (MES-like) tumor cells: MES-Hyp, colocalized with monocyte-derived brain macrophages in hypoxic regions; and MES-Ast, associated with endothelial cells, pericytes and vascular smooth muscle cells. We also predicted and experimentally verified cell subtypes and ligand–receptor pairs involved in intercellular communications in each cellular community. Furthermore, patch sequencing analysis revealed that synaptic connections with glioma cells were predominantly formed between neurons and oligodendrocyte-progenitor-like tumor cells. Overall, our study provides insights into the spatial organization and intercellular communication in GBM, offering potential therapeutic targets. Integrating spatial and single-cell data from 100 patients, the authors define conserved cellular communities and communications in glioblastoma, revealing distinct mesenchymal-like tumor subtypes and predominant neurogliomal synapses that shape tumor progression. [ABSTRACT FROM AUTHOR]
Copyright of Nature Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Spatial and single-cell characterization of human glioblastoma tumor microenvironment reveals malignant cellular communities.
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  Data: <searchLink fieldCode="AR" term="%22Lin%2C+Jun%22">Lin, Jun</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Chunpeng%22">Chen, Chunpeng</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Shouzhen%22">Li, Shouzhen</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Liu%22">Chen, Liu</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fang%2C+Minghao%22">Fang, Minghao</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fu%2C+Shuqi%22">Fu, Shuqi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Kaixing%22">Chen, Kaixing</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Xu%2C+Hao%22">Xu, Hao</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhang%2C+Fenghuan%22">Zhang, Fenghuan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Rirui%22">Wang, Rirui</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Jiang%2C+Chen%22">Jiang, Chen</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Tang%2C+Meifang%22">Tang, Meifang</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Liu%2C+Zitian%22">Liu, Zitian</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Shuyan%22">Wang, Shuyan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Liu%2C+Ke%22">Liu, Ke</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Niu%2C+Chaoshi%22">Niu, Chaoshi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Bin%22">Li, Bin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Liu%2C+Xu%22">Liu, Xu</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cheng%2C+Chuandong%22">Cheng, Chuandong</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Tang%2C+Ai-Hui%22">Tang, Ai-Hui</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Nature+Neuroscience%22">Nature Neuroscience</searchLink>. Jun2026, Vol. 29 Issue 6, p1342-1354. 13p.
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Understanding the complex cellular and spatial organization of glioblastoma (GBM) and its microenvironment is crucial for improving diagnosis and treatment. Here we integrated 121 spatial transcriptomics, single-cell RNA sequencing, single-cell assay for transposase-accessible chromatin using sequencing and patch sequencing profiles from 100 patients to characterize primary GBM tissue. We identified four malignant cellular communities that exhibited consistent patterns of cell-type compositions, gene expression and intercellular interactions across patients. We identified two subpopulations of mesenchymal-like (MES-like) tumor cells: MES-Hyp, colocalized with monocyte-derived brain macrophages in hypoxic regions; and MES-Ast, associated with endothelial cells, pericytes and vascular smooth muscle cells. We also predicted and experimentally verified cell subtypes and ligand–receptor pairs involved in intercellular communications in each cellular community. Furthermore, patch sequencing analysis revealed that synaptic connections with glioma cells were predominantly formed between neurons and oligodendrocyte-progenitor-like tumor cells. Overall, our study provides insights into the spatial organization and intercellular communication in GBM, offering potential therapeutic targets. Integrating spatial and single-cell data from 100 patients, the authors define conserved cellular communities and communications in glioblastoma, revealing distinct mesenchymal-like tumor subtypes and predominant neurogliomal synapses that shape tumor progression. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Nature Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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