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Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma
Cancer Cell ( IF 50.3 ) Pub Date : 2022-06-13 , DOI: 10.1016/j.ccell.2022.05.009
Vidhya M Ravi 1 , Paulina Will 2 , Jan Kueckelhaus 3 , Na Sun 4 , Kevin Joseph 5 , Henrike Salié 6 , Lea Vollmer 2 , Ugne Kuliesiute 7 , Jasmin von Ehr 2 , Jasim K Benotmane 2 , Nicolas Neidert 2 , Marie Follo 8 , Florian Scherer 8 , Jonathan M Goeldner 2 , Simon P Behringer 2 , Pamela Franco 9 , Mohammed Khiat 2 , Junyi Zhang 2 , Ulrich G Hofmann 10 , Christian Fung 11 , Franz L Ricklefs 12 , Katrin Lamszus 12 , Melanie Boerries 13 , Manching Ku 14 , Jürgen Beck 15 , Roman Sankowski 16 , Marius Schwabenland 16 , Marco Prinz 17 , Ulrich Schüller 18 , Saskia Killmer 6 , Bertram Bengsch 19 , Axel K Walch 4 , Daniel Delev 20 , Oliver Schnell 5 , Dieter Henrik Heiland 21
Affiliation  

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.



中文翻译:

空间分辨的多组学破译胶质母细胞瘤中的双向肿瘤-宿主相互依赖性

胶质母细胞瘤是中枢神经系统的恶性肿瘤,其特点是亚克隆多样性和发育等级中的动态适应。在这些肿瘤的空间背景下动态重组的来源仍然难以捉摸。在这里,我们通过空间分辨的转录组学、代谢组学和蛋白质组学来表征胶质母细胞瘤。通过破译患者之间区域共享的转录程序,我们推断胶质母细胞瘤是由谱系状态的空间分离组织的,并适应炎症和/或代谢刺激,让人联想到成熟星形胶质细胞的反应性转化。代谢成像和成像质谱流式细胞术的整合揭示了局部区域肿瘤宿主的相互依赖性,从而产生了空间专有的适应性转录程序。推断拷贝数改变强调与反应性转录程序相关的亚克隆的空间凝聚组织,证实环境压力会引起选择压力。将胶质母细胞瘤干细胞模型植入人类和啮齿动物新皮质组织,模拟各种环境,证实转录状态源于对各种环境的动态适应。

更新日期:2022-06-13
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