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Integrative spatial analysis reveals a multi-layered organization of glioblastoma.
- Source :
-
Cell [Cell] 2024 May 09; Vol. 187 (10), pp. 2485-2501.e26. Date of Electronic Publication: 2024 Apr 22. - Publication Year :
- 2024
-
Abstract
- Glioma contains malignant cells in diverse states. Here, we combine spatial transcriptomics, spatial proteomics, and computational approaches to define glioma cellular states and uncover their organization. We find three prominent modes of organization. First, gliomas are composed of small local environments, each typically enriched with one major cellular state. Second, specific pairs of states preferentially reside in proximity across multiple scales. This pairing of states is consistent across tumors. Third, these pairwise interactions collectively define a global architecture composed of five layers. Hypoxia appears to drive the layers, as it is associated with a long-range organization that includes all cancer cell states. Accordingly, tumor regions distant from any hypoxic/necrotic foci and tumors that lack hypoxia such as low-grade IDH-mutant glioma are less organized. In summary, we provide a conceptual framework for the organization of cellular states in glioma, highlighting hypoxia as a long-range tissue organizer.<br />Competing Interests: Declaration of interests I.T. is an advisory board member of Immunitas Therapeutics. M.L.S. is an equity holder, scientific co-founder, and advisory board member of Immunitas Therapeutics. Abcam provided carrier-free antibodies for CODEX experiments (to R.H.).<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Spatial Analysis
Transcriptome genetics
Tumor Microenvironment
Proteomics
Isocitrate Dehydrogenase genetics
Isocitrate Dehydrogenase metabolism
Gene Expression Regulation, Neoplastic
Glioblastoma pathology
Glioblastoma genetics
Glioblastoma metabolism
Brain Neoplasms pathology
Brain Neoplasms genetics
Brain Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 187
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 38653236
- Full Text :
- https://doi.org/10.1016/j.cell.2024.03.029