Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma
Ravi VM, Will P, Kueckelhaus J, Sun N, Joseph K, Salié H, Vollmer L, Kuliesiute U, von Ehr J, Benotmane JK, Neidert N, Follo M, Scherer F, Goeldner JM, Behringer SP, Franco P, Khiat M, Zhang J, Hofmann UG, Fung C, Ricklefs FL, Lamszus K, Boerries M, Ku M, Beck J, Sankowski R, Schwabenland M, Prinz M, Schüller U, Killmer S, Bengsch B, Walch AK, Delev D, Schnell O, Heiland DH (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Book Volume: 40
Pages Range: 639-655.e13
Journal Issue: 6
DOI: 10.1016/j.ccell.2022.05.009
Abstract
Glioblastomas are malignant tumors of the central nervous system hallmarked by subclonal diversity and dynamic adaptation amid developmental hierarchies. The source of dynamic reorganization within the spatial context of these tumors remains elusive. Here, we characterized glioblastomas by spatially resolved transcriptomics, metabolomics, and proteomics. By deciphering regionally shared transcriptional programs across patients, we infer that glioblastoma is organized by spatial segregation of lineage states and adapts to inflammatory and/or metabolic stimuli, reminiscent of the reactive transformation in mature astrocytes. Integration of metabolic imaging and imaging mass cytometry uncovered locoregional tumor-host interdependence, resulting in spatially exclusive adaptive transcriptional programs. Inferring copy-number alterations emphasizes a spatially cohesive organization of subclones associated with reactive transcriptional programs, confirming that environmental stress gives rise to selection pressure. A model of glioblastoma stem cells implanted into human and rodent neocortical tissue mimicking various environments confirmed that transcriptional states originate from dynamic adaptation to various environments.
Authors with CRIS profile
Involved external institutions
Universitätsklinikum Freiburg
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Albert-Ludwigs-Universität Freiburg
Germany (DE)
Universitätsklinikum Hamburg-Eppendorf (UKE)
Germany (DE)
Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen
Germany (DE)
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Albert-Ludwigs-Universität Freiburg
Germany (DE)
Universitätsklinikum Hamburg-Eppendorf (UKE)
Germany (DE)
Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen
Germany (DE)
How to cite
APA:
Ravi, V.M., Will, P., Kueckelhaus, J., Sun, N., Joseph, K., Salié, H.,... Heiland, D.H. (2022). Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma. Cancer Cell, 40(6), 639-655.e13. https://doi.org/10.1016/j.ccell.2022.05.009
MLA:
Ravi, Vidhya M., et al. "Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma." Cancer Cell 40.6 (2022): 639-655.e13.
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