Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma.
IF: 38.585
Cited by: 53


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.


Spatial Transcriptomics
genomic instability
glioblastoma heterogeneity
imaging mass cytometry
spatially resolved transcriptomics
tumor ecosystem

MeSH terms

Brain Neoplasms


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