文章：

幕上室管膜瘤异质性的多维分析

Multidimensional profiling of heterogeneity in supratentorial ependymomas

原文发布日期：2026-03-11

DOI: 10.1038/s41586-026-10214-2

类型: Article

开放获取: 是

英文摘要：

Supratentorial ependymomas are aggressive childhood brain cancers that retain features of neurodevelopmental cell types1 and segregate into molecularly and clinically distinct subgroups2,3, suggesting different developmental roots. The developmental signatures, as well as microenvironmental factors, underlying aberrant cellular transformation and behaviour across each supratentorial ependymoma subgroup are unclear. Here we integrated single-cell and spatial transcriptomics, as well as in vitro and in vivo live-cell imaging, to define supratentorial ependymoma cell states, spatial organization and dynamic behaviour within the neural microenvironment. We find that individual tumour subgroups have two distinct progenitor-like cell states—neuroepithelial-like and embryonic-like—that are reminiscent of early human brain development and diverge in the extent of their neuronal or ependymal differentiation. We further identify several modes of spatial organization of these tumours, including a high-order architecture that is influenced by mesenchymal and hypoxia signatures, and local neighbourhood structures. Finally, we identify a role for brain-resident cells in shifting supratentorial ependymoma cellular heterogeneity towards neuronal-like cells that co-opt immature neuronal morphology and migratory mechanisms, and a subset of neuroepithelial-like cells that are both proliferative and highly migratory. Collectively, these findings provide a multidimensional framework to integrate transcriptional and phenotypic characterization of tumour heterogeneity in supratentorial ependymoma and its potential clinical implications.

摘要翻译： 

幕上室管膜瘤是一种侵袭性的儿童脑癌，其保留了神经发育细胞类型的特征1，并可分为分子和临床特征各异的亚群2,3，提示其具有不同的发育起源。目前尚不清楚每个幕上室管膜瘤亚群中驱动异常细胞转化和行为的发育特征及微环境因素。本研究通过整合单细胞和空间转录组学，以及体外和体内活细胞成像技术，揭示了幕上室管膜瘤的细胞状态、空间组织方式及其在神经微环境中的动态行为。我们发现不同肿瘤亚群存在两种独特的祖细胞样状态——神经上皮样和胚胎样——这两种状态与人类早期大脑发育特征相似，并在神经元或室管膜细胞分化程度上存在差异。我们进一步确定了这些肿瘤的多种空间组织模式，包括受间充质和缺氧特征影响的层级结构以及局部邻域结构。最后，我们发现脑驻留细胞可促使幕上室膜瘤细胞异质性向神经元样细胞转化，这些细胞呈现出未成熟神经元的形态并利用其迁移机制，同时发现部分具有增殖能力和高度迁移性的神经上皮样细胞。这些发现共同构建了一个多维度框架，有助于整合幕上室管膜瘤肿瘤异质性的转录和表型特征及其潜在的临床意义。

原文链接：

Multidimensional profiling of heterogeneity in supratentorial ependymomas