脑膜孤立性纤维瘤（SFT）是罕见的间叶性肿瘤，与局部复发和血行转移相关。脑膜 SFT 独特临床行为背后的细胞状态和空间转录组结构尚不清楚。使用单细胞 (n=4)、空间 (n=8) 和批量 RNA 测序 (n=22) 来定义细胞状态以及跨组织学级别和患者匹配的原发/复发或颅内/转移样本对中脑膜 SFT 的空间转录组结构。使用免疫荧光、免疫组织化学以及单细胞类型与脑膜瘤或脑血管发育或稳态的比较进行验证。在这里，我们显示脑膜 SFT 由区域不同的基因表达程序组成，类似于脑血管发育或稳态。单细胞轨迹分析和单细胞的伪时间排序表明，脑膜 SFT 细胞的命运决定是动态的和可互换的。细胞间通讯分析证明了整个脑膜 SFT 微环境中受体-配体的相互作用，特别是 SFT 细胞、内皮细胞和未成熟神经元之间的相互作用。脑膜 SFT 与脑膜瘤单细胞转录组的直接比较表明，SFT 细胞内皮标记物表达丰富，而脑膜瘤细胞壁细胞标记物表达丰富。脑膜 SFT 空间转录组在 WHO 组织学分级以及患者匹配的原发性/复发性或颅内/转移性样本对中，在细胞状态、基因表达程序和细胞间相互作用方面显示出区域不同的肿瘤内异质性。这些结果揭示了脑膜的潜在途径SFT 生物学与其他中枢神经系统肿瘤进行比较，并提供了一个整合人类癌症和正常组织的单细胞、空间和批量 RNA 测序数据的框架。© 作者 2024。由牛津大学出版社代表神经肿瘤学会。版权所有。如需商业重复使用，请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限都可以通过我们网站文章页面上的权限链接通过我们的 RightsLink 服务获得 - 如需了解更多信息，请联系journals.permissions@oup.com。

Meningeal solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that are associated with local recurrence and hematogenous metastasis. The cell states and spatial transcriptomic architecture underlying the unique clinical behavior of meningeal SFTs are unknown.Single-cell (n=4), spatial (n=8), and bulk RNA sequencing (n=22) was used to define the cell states and spatial transcriptomic architecture of meningeal SFTs across histological grades and in patient-matched pairs of primary/recurrent or intracranial/metastatic samples. Immunofluorescence, immunohistochemistry, and comparison of single-cell types to meningiomas, or to cerebral vascular development or homeostasis, were used for validation.Here we show meningeal SFTs are comprised of regionally distinct gene expression programs that resemble cerebral vascular development or homeostasis. Single-cell trajectory analysis and pseudotemporal ordering of single-cells suggest that meningeal SFT cell fate decisions are dynamic and interchangeable. Cell-cell communication analyses demonstrate receptor-ligand interactions throughout the meningeal SFT microenvironment, particularly between SFT cells, endothelia, and immature neurons. Direct comparison of single-cell transcriptomes from meningeal SFTs versus meningiomas shows that SFT cells are enriched in expression of endothelial markers while meningiomas cells are enriched in expression of mural cells markers. Meningeal SFT spatial transcriptomes show regionally distinct intratumor heterogeneity in cell states, gene expression programs, and cell-cell interactions across WHO histological grades and in patient-matched pairs of primary/recurrent or intracranial/metastatic samples.These results shed light on pathways underlying meningeal SFT biology in comparison to other central nervous system tumors and provide a framework for integrating single-cell, spatial, and bulk RNA sequencing data across human cancers and normal tissues.© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.