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Ravi, V.M.* ; Will, P.* ; Kueckelhaus, J.* ; Sun, N. ; Joseph, K.* ; Salié, H.* ; Vollmer, L.* ; Kuliesiute, U.* ; von Ehr, J.* ; Benotmane, J.K.* ; Neidert, N.* ; Follo, M.* ; Scherer, F.* ; Goeldner, J.M.* ; Behringer, S.P.* ; Franco, P.* ; Khiat, M.* ; Zhang, J.* ; Hofmann, U.G.* ; Fung, C.* ; Ricklefs, F.L.* ; Lamszus, K.* ; Boerries, M.* ; Ku, M.C.* ; Beck, J.* ; Sankowski, R.* ; Schwabenland, M.* ; Prinz, M.* ; Schüller, U.* ; Killmer, S.* ; Bengsch, B.* ; Walch, A.K. ; Delev, D.* ; Schnell, O.* ; Heiland, D.H.*

Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma.

Cancer Cell 40, 639-655.e13 (2022)

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	Open Access Gold (Paid Option)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Genomic Instability ; Glioblastoma Heterogeneity ; Imaging Mass Cytometry ; Maldi ; Microenvironment ; Multiomics ; Spatially Resolved Transcriptomics ; Tumor Ecosystem

ISSN (print) / ISBN 1535-6108

e-ISSN 1878-3686

Journal Cancer Cell

Quellenangaben Volume: 40, Issue: 6, Pages: 639-655.e13

Publisher Cell Press

Publishing Place Cambridge, Mass.

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Research Unit Analytical Pathology (AAP)

Grants Fördergemeinschaft Kinderkrebs-Zentrum Hamburg
Else Kroner-Fresenius-Stiftung
Deutsche Forschungsgemeinschaft
MEPHISTO
Bundes Ministerium für Bildung und Forschung