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

Brain Neoplasms / pathology Glioblastoma / pathology Humans Metabolomics / methods
MALDI genomic instability glioblastoma heterogeneity imaging mass cytometry microenvironment multiomics spatially resolved transcriptomics tumor ecosystem

Journal

Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617

Informations de publication

Date de publication:
13 06 2022
Historique:
received: 04 06 2021
revised: 30 09 2021
accepted: 13 05 2022
entrez: 14 6 2022
pubmed: 15 6 2022
medline: 18 6 2022
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.ccell.2022.05.009 PMID: 35700707
pubmed: 35700707
pii: S1535-6108(22)00220-3
doi: 10.1016/j.ccell.2022.05.009
pii:
doi:

Banques de données

Dryad
['10.5061/dryad.h70rxwdmj']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

639-655.e13

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Vidhya M Ravi (VM)

Microenvironment and Immunology Research Laboratory, Medical Center - University of Freiburg, Freiburg, Germany; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Translational NeuroOncology Research Group, Medical Center - University of Freiburg, Freiburg, Germany; Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg, Germany; Center of Advanced Surgical Tissue Analysis (CAST), University of Freiburg, Freiburg, Germany.

Paulina Will (P)

Microenvironment and Immunology Research Laboratory, Medical Center - University of Freiburg, Freiburg, Germany; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Translational NeuroOncology Research Group, Medical Center - University of Freiburg, Freiburg, Germany.

Jan Kueckelhaus (J)

Microenvironment and Immunology Research Laboratory, Medical Center - University of Freiburg, Freiburg, Germany; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Translational NeuroOncology Research Group, Medical Center - University of Freiburg, Freiburg, Germany; Neurosurgical Artificial Intelligence Laboratory Aachen (NAILA), Department of Neurosurgery, RWTH University of Aachen, Aachen, Germany.

Na Sun (N)

Research Unit Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany.

Kevin Joseph (K)

Microenvironment and Immunology Research Laboratory, Medical Center - University of Freiburg, Freiburg, Germany; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Translational NeuroOncology Research Group, Medical Center - University of Freiburg, Freiburg, Germany; Center of Advanced Surgical Tissue Analysis (CAST), University of Freiburg, Freiburg, Germany.

Henrike Salié (H)

Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of Medicine II: Gastroenterology, Hepatology, Endocrinology, and Infectious Disease, Medical Center - University of Freiburg, Freiburg, Germany.

Lea Vollmer (L)

Microenvironment and Immunology Research Laboratory, Medical Center - University of Freiburg, Freiburg, Germany; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Translational NeuroOncology Research Group, Medical Center - University of Freiburg, Freiburg, Germany.

Ugne Kuliesiute (U)

Microenvironment and Immunology Research Laboratory, Medical Center - University of Freiburg, Freiburg, Germany; Translational NeuroOncology Research Group, Medical Center - University of Freiburg, Freiburg, Germany; The Institute of Biosciences, Life Sciences Center, Vilnius University, Vilnius, Lithuania.

Jasmin von Ehr (J)

Microenvironment and Immunology Research Laboratory, Medical Center - University of Freiburg, Freiburg, Germany; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Translational NeuroOncology Research Group, Medical Center - University of Freiburg, Freiburg, Germany.

Jasim K Benotmane (JK)

Microenvironment and Immunology Research Laboratory, Medical Center - University of Freiburg, Freiburg, Germany; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Translational NeuroOncology Research Group, Medical Center - University of Freiburg, Freiburg, Germany.

Nicolas Neidert (N)

Microenvironment and Immunology Research Laboratory, Medical Center - University of Freiburg, Freiburg, Germany; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Translational NeuroOncology Research Group, Medical Center - University of Freiburg, Freiburg, Germany.

Marie Follo (M)

Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of Medicine I, Medical Center - University of Freiburg, Freiburg, Germany.

Florian Scherer (F)

Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of Medicine I, Medical Center - University of Freiburg, Freiburg, Germany.

Jonathan M Goeldner (JM)

Microenvironment and Immunology Research Laboratory, Medical Center - University of Freiburg, Freiburg, Germany; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Translational NeuroOncology Research Group, Medical Center - University of Freiburg, Freiburg, Germany.

Simon P Behringer (SP)

Microenvironment and Immunology Research Laboratory, Medical Center - University of Freiburg, Freiburg, Germany; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Translational NeuroOncology Research Group, Medical Center - University of Freiburg, Freiburg, Germany.

Pamela Franco (P)

Faculty of Medicine, University of Freiburg, Freiburg, Germany; Translational NeuroOncology Research Group, Medical Center - University of Freiburg, Freiburg, Germany.

Mohammed Khiat (M)

Microenvironment and Immunology Research Laboratory, Medical Center - University of Freiburg, Freiburg, Germany; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Translational NeuroOncology Research Group, Medical Center - University of Freiburg, Freiburg, Germany.

Junyi Zhang (J)

Microenvironment and Immunology Research Laboratory, Medical Center - University of Freiburg, Freiburg, Germany; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Translational NeuroOncology Research Group, Medical Center - University of Freiburg, Freiburg, Germany.

Ulrich G Hofmann (UG)

Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Neuroelectronic Systems, Medical Center - University of Freiburg, Freiburg, Germany.

Christian Fung (C)

Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Franz L Ricklefs (FL)

Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany; Laboratory for Brain Tumor Biology, University Hospital Eppendorf, Hamburg, Germany.

Katrin Lamszus (K)

Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany; Laboratory for Brain Tumor Biology, University Hospital Eppendorf, Hamburg, Germany.

Melanie Boerries (M)

Faculty of Medicine, University of Freiburg, Freiburg, Germany; Institute of Medical Bioinformatics and Systems Medicine, Medical Center-University of Freiburg, Freiburg, Germany; Comprehensive Cancer Center Freiburg (CCCF), Medical Center - University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), partner site Freiburg, Freiburg, Germany.

Manching Ku (M)

Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center - University of Freiburg, Freiburg, Germany.

Jürgen Beck (J)

Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Center for NeuroModulation (NeuroModul), University of Freiburg, Freiburg, Germany; Center of Advanced Surgical Tissue Analysis (CAST), University of Freiburg, Freiburg, Germany.

Roman Sankowski (R)

Faculty of Medicine, University of Freiburg, Freiburg, Germany; Institute of Neuropathology, Medical Center - University of Freiburg, Freiburg, German.

Marius Schwabenland (M)

Faculty of Medicine, University of Freiburg, Freiburg, Germany; Institute of Neuropathology, Medical Center - University of Freiburg, Freiburg, German.

Marco Prinz (M)

Faculty of Medicine, University of Freiburg, Freiburg, Germany; Center for NeuroModulation (NeuroModul), University of Freiburg, Freiburg, Germany; Institute of Neuropathology, Medical Center - University of Freiburg, Freiburg, German; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.

Ulrich Schüller (U)

Institute of Neuropathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; Research Institute Children's Cancer Center, Hamburg, Germany; Department of Pediatric Hematology and Oncology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Saskia Killmer (S)

Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of Medicine II: Gastroenterology, Hepatology, Endocrinology, and Infectious Disease, Medical Center - University of Freiburg, Freiburg, Germany.

Bertram Bengsch (B)

Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of Medicine II: Gastroenterology, Hepatology, Endocrinology, and Infectious Disease, Medical Center - University of Freiburg, Freiburg, Germany; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.

Axel K Walch (AK)

Research Unit Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany.

Daniel Delev (D)

Neurosurgical Artificial Intelligence Laboratory Aachen (NAILA), Department of Neurosurgery, RWTH University of Aachen, Aachen, Germany; Department of Neurosurgery, RWTH University of Aachen, Aachen, Germany.

Oliver Schnell (O)

Microenvironment and Immunology Research Laboratory, Medical Center - University of Freiburg, Freiburg, Germany; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Translational NeuroOncology Research Group, Medical Center - University of Freiburg, Freiburg, Germany; Center of Advanced Surgical Tissue Analysis (CAST), University of Freiburg, Freiburg, Germany.

Dieter Henrik Heiland (DH)

Microenvironment and Immunology Research Laboratory, Medical Center - University of Freiburg, Freiburg, Germany; Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Comprehensive Cancer Center Freiburg (CCCF), Medical Center - University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), partner site Freiburg, Freiburg, Germany; Center of Advanced Surgical Tissue Analysis (CAST), University of Freiburg, Freiburg, Germany. Electronic address: dieter.henrik.heiland@uniklinik-freiburg.de.

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Classifications MeSH

questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › Spatially resolved multi-omics deciphers...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Gliome › Astrocytome › Glioblastome › Spatially resolved multi-omics deciphers...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Spatially resolved multi-omics deciphers...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Métabolomique › Spatially resolved multi-omics deciphers...