# Integrative spatial analysis reveals a multi-layered organization of glioblastoma

Article · Greenwald AC, Darnell NG, Hoefflin R, Simkin D, Mount CW, Gonzalez Castro LN, Harnik Y, Dumont S, Hirsch D, Nomura M, Talpir T, Kedmi M, Goliand I, Medici G, Laffy J, Li B, Mangena V, Keren-Shaul H, Weller M, Addadi Y, Neidert MC, Suvà ML, Tirosh I

- Archive id: doi:10.1016/j.cell.2024.03.029
- Published: 2024-04-22
- Venue: Cell
- DOI: https://doi.org/10.1016/j.cell.2024.03.029
- PMID: 38653236
- PMCID: PMC11088502
- Citations: 365
- Source URL: https://doi.org/10.1016/j.cell.2024.03.029
- PDF: https://europepmc.org/articles/PMC11088502/pdf
- Provenance: europepmc

## 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.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Single-Cell & Spatial Omics](https://space-kitty.com/topics/single-cell-spatial)

Cited in dossiers:
- [Single-Cell & Spatial Omics: State of the Field (October 2026)](https://space-kitty.com/dossiers/single-cell-spatial)

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