德国弗莱堡大学Dieter Henrik Heiland研究团队利用空间分辨多组学破译了恶性胶质瘤中肿瘤-宿主双向相互依赖关系。这一研究成果发表在2022年6月13日出版的国际学术期刊《癌细胞》上。

他们通过空间分辨转录组学、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，他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。

据介绍，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。枢神经系统的恶性肿瘤，具有亚克隆多样性和发育层次的动态适应性。这些肿瘤在空间范围内的动态重组的能力仍然很弱。

附：英文原文

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

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

Issue&Volume: 2022/06/13

Abstract: 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.

DOI: 10.1016/j.ccell.2022.05.009

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00220-3