以色列雷霍沃特魏茨曼科学研究院Itay Tirosh和美国哈佛医学院Mario L. Suvà共同合作，近期取得重要工作进展。他们通过综合空间分析揭示胶质母细胞瘤具有多层组织结构。相关研究成果2024年4月22日在线发表于《细胞》杂志上。
研究人员介绍，胶质瘤包含不同状态的恶性细胞。
研究人员结合了空间转录组学、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。研究人员发现了三种突出的组织模式。首先，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，特定的几对状态在多个尺度上优先靠近。这种状态配对在不同肿瘤中是一致的。第三，这些成对的交互共同定义了一个由五层组成的全局架构。缺氧似乎驱动了这些层，因为它与包括所有癌症细胞状态的长期组织有关。因此，远离任何缺氧/坏死灶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）组织较少。
总之，这一研究为神经胶质瘤细胞状态的组织提供了一个概念框架，强调缺氧是一种长期组织组织者。
附：英文原文
Title: Integrative spatial analysis reveals a multi-layered organization of glioblastoma
Author: Alissa C. Greenwald, Noam Galili Darnell, Rouven Hoefflin, Dor Simkin, Christopher W. Mount, L. Nicolas Gonzalez Castro, Yotam Harnik, Sydney Dumont, Dana Hirsch, Masashi Nomura, Tom Talpir, Merav Kedmi, Inna Goliand, Gioele Medici, Julie Laffy, Baoguo Li, Vamsi Mangena, Hadas Keren-Shaul, Michael Weller, Yoseph Addadi, Marian C. Neidert, Mario L. Suvà, Itay Tirosh
Issue&Volume: 2024-04-22
Abstract: Glioma contains malignant cells in diverse states. Here, we combine spatial transcriptomics,spatial proteomics, and computational approaches to define glioma cellular statesand uncover their organization. We find three prominent modes of organization. First,gliomas are composed of small local environments, each typically enriched with onemajor cellular state. Second, specific pairs of states preferentially reside in proximityacross multiple scales. This pairing of states is consistent across tumors. Third,these pairwise interactions collectively define a global architecture composed offive layers. Hypoxia appears to drive the layers, as it is associated with a long-rangeorganization that includes all cancer cell states. Accordingly, tumor regions distantfrom any hypoxic/necrotic foci and tumors that lack hypoxia such as low-grade IDH-mutantglioma are less organized. In summary, we provide a conceptual framework for the organizationof cellular states in glioma, highlighting hypoxia as a long-range tissue organizer.
DOI: 10.1016/j.cell.2024.03.029
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00320-9