Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Cell. 2024 May 9;187(10):2485-2501.e26. doi: 10.1016/j.cell.2024.03.029. Epub 2024 Apr 22.
Glioma contains malignant cells in diverse states. Here, we combine spatial transcriptomics, spatial proteomics, and computational approaches to define glioma cellular states and uncover their organization. We find three prominent modes of organization. First, gliomas are composed of small local environments, each typically enriched with one major cellular state. Second, specific pairs of states preferentially reside in proximity across multiple scales. This pairing of states is consistent across tumors. Third, these pairwise interactions collectively define a global architecture composed of five layers. Hypoxia appears to drive the layers, as it is associated with a long-range organization that includes all cancer cell states. Accordingly, tumor regions distant from any hypoxic/necrotic foci and tumors that lack hypoxia such as low-grade IDH-mutant glioma are less organized. In summary, we provide a conceptual framework for the organization of cellular states in glioma, highlighting hypoxia as a long-range tissue organizer.
神经胶质瘤包含处于不同状态的恶性细胞。在这里，我们结合空间转录组学、空间蛋白质组学和计算方法来定义神经胶质瘤细胞状态并揭示其组织方式。我们发现了三种主要的组织方式。首先，神经胶质瘤由小的局部环境组成，每个环境通常富含一种主要的细胞状态。其次，特定的两种状态优先在多个尺度上接近存在。这种状态对在肿瘤之间是一致的。第三，这些成对的相互作用共同定义了一个由五层组成的全局结构。缺氧似乎驱动了这些层，因为它与包括所有癌细胞状态的长程组织有关。因此，远离任何缺氧/坏死焦点的肿瘤区域和缺乏缺氧的肿瘤（如低级别 IDH 突变型神经胶质瘤）组织性较差。总之，我们提供了一个神经胶质瘤中细胞状态组织的概念框架，强调了缺氧作为一种长程组织调节剂的作用。
