Spatially Resolved Multi-Omics Deciphers Bidirectional Tumor-Host Interdependence in Glioblastoma

Ravi, Vidhya; Will, Paulina; Kueckelhaus, Jan; Sun, Na; Joseph, Kevin; Salié, Henrike; Vollmer, Lea; Kuliesiute, Ugne; Ehr, Jasmin von; Benotmane, Jasim Kada; Neidert, Nicolas; Follo, Marie; Scherer, Florian; Goeldner, Jonathan M; Behringer, Sidney; Franco, Pamela; Khiat, Mohammed; Zhang, Junyi; Hofmann, Ulrich; Fung, Christian; Lamszus, Katrin; Boerries, Melanie; Ku, Manching; Beck, Jürgen; Sankowski, Roman; Schwabenland, Marius; Prinz, Marco; Schüller, Ulrich; Killmer, Saskia; Bengsch, Bertram; Walch, Axel; Delev, Daniel; Schnell, Oliver; Heiland, Dieter Henrik

doi:10.2139/ssrn.3865275

Cited by 13 publications

(36 citation statements)

References 13 publications

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“…This likely reflects how cells are arranged within the tumor and who their neighbors are. Recent spatial scrutiny of GB tissues deciphered distinct transcriptional states, ranging from progenitor/development-like to reactive immune- and hypoxia-related programs (Ravi et al, 2022). Precise mapping of the cellular localization of the TME components using the GBmap could help to refine the tumor structure and delineate cellular crosstalk between tissue neighborhoods ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We downloaded from the 10x Genomics website a publicly available GB sample profiled using the Visium ST platform (https://www.10xgenomics.com/resources/datasets/human-glioblastoma-whole-transcriptome-analysis-1-standard-1-2-0), as well as nine high-quality GB tissues profiled on the Visium platform (Ravi et al, 2022). Data importing, basic filtering of spots based on total counts and expressed genes, normalization, dimensional reduction, clustering, and detection of spatially variable features were performed in Python using the Scanpy package (Wolf et al, 2018).…”

Section: Methodsmentioning

confidence: 99%

“…However, they were either limited to small sample size or did not provide a holistic overview of the GB cellular composition to construct the tumor interactome. Additionally, despite current technological advances, transcriptomic profiling in a spatially resolved manner has only lately been used to explore GB (Ravi et al, 2021; Ravi et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

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Harmonized single-cell landscape, intercellular crosstalk and tumor architecture of glioblastoma

Ruiz-Moreno

Salas

Samuelsson

et al. 2022

Preprint

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Glioblastoma, isocitrate dehydrogenase (IDH)-wildtype (hereafter, GB), is an aggressive brain malignancy associated with a dismal prognosis and poor quality of life. Single-cell RNA sequencing has helped to grasp the complexity of the cell states and dynamic changes in GB. Large-scale data integration can help to uncover unexplored tumor pathobiology. Here, we resolved the composition of the tumor milieu and created a cellular map of GB ("GBmap"), a curated resource that harmonizes 26 datasets gathering 240 patients and spanning over 1.1 million cells. We showcase the applications of our resource for reference mapping, transfer learning, and biological discoveries. Our results uncover the sources of pro-angiogenic signaling and the multifaceted role of mesenchymal-like cancer cells. Reconstructing the tumor architecture using spatially resolved transcriptomics unveiled a high level of well-structured neoplastic niches. The GBmap represents a framework that allows the streamlined integration and interpretation of new data and provides a platform for exploratory analysis, hypothesis generation and testing.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Harmonized single-cell landscape, intercellular crosstalk and tumor architecture of glioblastoma

Ruiz-Moreno

Salas

Samuelsson

et al. 2022

Preprint

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“…Recent evidence indicates that this might be the case; data highlighting the contribution of injury programs to tumor heterogeneity have found that the injury-associated genes expressed in glioblastoma show significant overlap with those associated with a reactive astrocyte state [12,74]. This reactive AC-like state corresponds to MES-like signatures described in the wider literature [7,12,33,75], suggesting that the MES-like state encompasses cells which have activated latent reactive programs in response to microenvironmental stressors [37].…”

Section: Reactive Astrocytic Processes Are Echoed In Glioblastomamentioning

confidence: 87%

“…Indeed, recent single-cell RNA sequencing (scRNA-seq) analyses of human glioblastoma found that injury-associated inflammatory and wound-response signatures account for much of the transcriptional heterogeneity in glioblastoma [12]. Furthermore, spatially separated injury-associated microenvironmental stimuli including hypoxia, immune infiltration, and white matter damage have all been implicated in steering cell fate, as determined by recent spatially resolved transcriptomic, metabolomic, and proteomic analyses, as well as by bulk RNA-seq or scRNA-seq from distinct tumor regions [13,37,38] (Figure 1). These processes will be the focus of the following sections.…”

Section: Highlightsmentioning

confidence: 99%

Injury programs shape glioblastoma

Brooks

Ragdale²,

Hill³

et al. 2022

Trends in Neurosciences

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Tapirira guianensis is Selectively Cytotoxic, Induces Apoptosis to the Glioblastoma and Decreases Tumor Growth and Angiogenesis in vivo

Oliveira,

Rocha,

de Azevedo

et al. 2023

Planta Med

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Glioblastoma is the most frequent primary malignant brain tumor without effective treatment, which makes this work extremely relevant. The study of the bioactive compounds from medicinal plants plays an important role in the discovery of new drugs.This research investigated the constituents of Tapirira guianensis and its antitumor potential (in vitro and in vivo) in glioblastoma. The T. guianensis extracts were characterized by mass spectrometry. The ethyl acetate partition (01ID) and its fractions 01ID-F2 and 01ID-F4 from T. guianensis showed potential antitumor treatment evidenced by selective cytotoxicity for GAMG with IC50 14.1 µg/mL, 83.07 µg/mL, 59.27 µg/mL and U251 with IC50 25.92 µg/mL, 37.3 µg/mL and 18.84 µg/mL. Fractions 01ID-F2 and 01ID-F4 were 10 times more selective when compared to TMZ and 01ID for the two evaluated cell lines. T. guianensis also reduced matrix metalloproteinases 2 – 01ID-F2 (21.84%), 01ID-F4 (29.6%) and 9 – 01ID-F4 (73.42%), ID-F4 (53.84%) activities, and induced apoptosis mainly through the extrinsic pathway. Furthermore, all treatments significantly reduced tumor size (01ID p < 0,01, 01ID-F2 p < 0,01 and 01ID-F4 p < 0,0001) and caused blood vessels to shrink in vivo. The present findings highlight that T. guianensis exhibits considerable antitumor potential in preclinical studies of glioblastoma. This ability may be related to the phenolic compounds and sesquiterpene derivatives identified in the extracts. This study deserves further in vivo research, followed by clinical investigation.

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Spatially Resolved Multi-Omics Deciphers Bidirectional Tumor-Host Interdependence in Glioblastoma

Cited by 13 publications

References 13 publications

Harmonized single-cell landscape, intercellular crosstalk and tumor architecture of glioblastoma

Harmonized single-cell landscape, intercellular crosstalk and tumor architecture of glioblastoma

Injury programs shape glioblastoma

Tapirira guianensis is Selectively Cytotoxic, Induces Apoptosis to the Glioblastoma and Decreases Tumor Growth and Angiogenesis in vivo

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