Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma
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Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma. / Ravi, Vidhya M; Will, Paulina; Kueckelhaus, Jan; Sun, Na; Joseph, Kevin; Salié, Henrike; Vollmer, Lea; Kuliesiute, Ugne; von Ehr, Jasmin; Benotmane, Jasim K; Neidert, Nicolas; Follo, Marie; Scherer, Florian; Goeldner, Jonathan M; Behringer, Simon P; Franco, Pamela; Khiat, Mohammed; Zhang, Junyi; Hofmann, Ulrich G; Fung, Christian; Ricklefs, Franz L; Lamszus, Katrin; Boerries, Melanie; Ku, Manching; Beck, Jürgen; Sankowski, Roman; Schwabenland, Marius; Prinz, Marco; Schüller, Ulrich; Killmer, Saskia; Bengsch, Bertram; Walch, Axel K; Delev, Daniel; Schnell, Oliver; Heiland, Dieter Henrik.
In: CANCER CELL, Vol. 40, No. 6, 13.06.2022, p. 639-655.e13.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma
AU - Ravi, Vidhya M
AU - Will, Paulina
AU - Kueckelhaus, Jan
AU - Sun, Na
AU - Joseph, Kevin
AU - Salié, Henrike
AU - Vollmer, Lea
AU - Kuliesiute, Ugne
AU - von Ehr, Jasmin
AU - Benotmane, Jasim K
AU - Neidert, Nicolas
AU - Follo, Marie
AU - Scherer, Florian
AU - Goeldner, Jonathan M
AU - Behringer, Simon P
AU - Franco, Pamela
AU - Khiat, Mohammed
AU - Zhang, Junyi
AU - Hofmann, Ulrich G
AU - Fung, Christian
AU - Ricklefs, Franz L
AU - Lamszus, Katrin
AU - Boerries, Melanie
AU - Ku, Manching
AU - Beck, Jürgen
AU - Sankowski, Roman
AU - Schwabenland, Marius
AU - Prinz, Marco
AU - Schüller, Ulrich
AU - Killmer, Saskia
AU - Bengsch, Bertram
AU - Walch, Axel K
AU - Delev, Daniel
AU - Schnell, Oliver
AU - Heiland, Dieter Henrik
N1 - Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2022/6/13
Y1 - 2022/6/13
N2 - 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.
AB - 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.
KW - Brain Neoplasms/pathology
KW - Glioblastoma/pathology
KW - Humans
KW - Metabolomics/methods
U2 - 10.1016/j.ccell.2022.05.009
DO - 10.1016/j.ccell.2022.05.009
M3 - SCORING: Journal article
C2 - 35700707
VL - 40
SP - 639-655.e13
JO - CANCER CELL
JF - CANCER CELL
SN - 1535-6108
IS - 6
ER -