Publikation

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

Wissenschaftlicher Artikel/Review - 22.04.2024

Bereiche
PubMed
DOI
Kontakt

Zitation
Greenwald A, Darnell N, Hoefflin R, Simkin D, Mount C, Gonzalez Castro L, 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 M, Suvà M, Tirosh I. Integrative spatial analysis reveals a multi-layered organization of glioblastoma. Cell 2024; 187:2485-2501.e26.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Cell 2024; 187
Veröffentlichungsdatum
22.04.2024
eISSN (Online)
1097-4172
Seiten
2485-2501.e26
Kurzbeschreibung/Zielsetzung

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.