恶性胶质瘤是无法治愈的脑部肿瘤，其预后极差，几乎总是以死亡告终，尽管在过去二十年中投入了数十亿美元进行了大量的研究和临床试验，但治疗进展微乎其微。许多胶质瘤的研究利用了不同的组织学和基因组平台来描述胶质瘤中令人惊叹的基因组、转录组和免疫组织学多样性。单细胞和空间组学技术能够前所未有地描述实体恶性肿瘤的多样性，并以有限的手术切除组织提供了转录、表观遗传和微环境状态的精细注释。在最广泛的层面上，胶质瘤的多样性可以被定义为外表上由表观遗传改变（IDH和组蛋白突变型）驱动的肿瘤与非表观遗传肿瘤（IDH野生型）之间的区别。表观遗传驱动的肿瘤以显著的转录程序、免疫学上独特的微环境和尚未完全理解的拓扑结构（独特的细胞邻域和细胞间相互作用）来定义。因此，这些肿瘤是单细胞多组学技术的理想基质，用以解析肿瘤内的复杂特征，包括分化轨迹、肿瘤免疫细胞相互作用和染色质失调。本综述总结了单细胞多组学技术在已有的表观遗传驱动胶质瘤数据集中的应用。更重要的是，我们讨论了新型多组学策略的未来能力和应用，以回答未解决的问题、促进强大的治疗策略的发展，并通过数字病理学改进个体化诊断和治疗。© 作者2023年发表。由牛津大学出版社、神经肿瘤学学会和欧洲神经肿瘤学协会发表。

Malignant gliomas are incurable brain neoplasms with dismal prognoses and near-universal fatality, with minimal therapeutic progress despite billions of dollars invested in research and clinical trials over the last 2 decades. Many glioma studies have utilized disparate histologic and genomic platforms to characterize the stunning genomic, transcriptomic, and immunologic heterogeneity found in gliomas. Single-cell and spatial omics technologies enable unprecedented characterization of heterogeneity in solid malignancies and provide a granular annotation of transcriptional, epigenetic, and microenvironmental states with limited resected tissue. Heterogeneity in gliomas may be defined, at the broadest levels, by tumors ostensibly driven by epigenetic alterations (IDH- and histone-mutant) versus non-epigenetic tumors (IDH-wild type). Epigenetically driven tumors are defined by remarkable transcriptional programs, immunologically distinct microenvironments, and incompletely understood topography (unique cellular neighborhoods and cell-cell interactions). Thus, these tumors are the ideal substrate for single-cell multiomic technologies to disentangle the complex intra-tumoral features, including differentiation trajectories, tumor-immune cell interactions, and chromatin dysregulation. The current review summarizes the applications of single-cell multiomics to existing datasets of epigenetically driven glioma. More importantly, we discuss future capabilities and applications of novel multiomic strategies to answer outstanding questions, enable the development of potent therapeutic strategies, and improve personalized diagnostics and treatment via digital pathology.© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.