Mirchia Kanish, Choudhury Abrar, Joseph Tara, Birrueta Janeth Ochoa, Phillips Joanna J, Bhaduri Aparna, Crouch Elizabeth E, Perry Arie, Raleigh David R
Department of Pathology, University of California San Francisco, San Francisco, California, USA.
Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Neuro Oncol. 2025 Jan 12;27(1):155-166. doi: 10.1093/neuonc/noae172.
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) were 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. A direct comparison of single-cell transcriptomes from meningeal SFTs versus meningiomas shows that SFT cells are enriched in the expression of endothelial markers while meningioma cells are enriched in the expression of mural cell markers. Meningeal SFT spatial transcriptomes show regionally distinct intratumor heterogeneity in cell states, gene expression programs, and cell-cell interactions across World Health Organization 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.
脑膜孤立性纤维瘤（SFTs）是罕见的间叶性肿瘤，与局部复发和血行转移相关。脑膜SFTs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。
采用单细胞（n = 4）、空间（n = 8）和批量RNA测序（n = 22）来确定脑膜SFTs在不同组织学分级以及患者匹配的原发/复发或颅内/转移样本对中的细胞状态和空间转录组结构。免疫荧光、免疫组织化学以及将单细胞类型与脑膜瘤、脑血管发育或内环境稳定进行比较，用于验证。
我们在此表明，脑膜SFTs由类似于脑血管发育或内环境稳定的区域特异性基因表达程序组成。单细胞轨迹分析和单细胞的伪时间排序表明，脑膜SFT细胞命运决定是动态且可互换的。细胞间通讯分析显示，在整个脑膜SFT微环境中存在受体 - 配体相互作用，特别是在SFT细胞、内皮细胞和未成熟神经元之间。脑膜SFT与脑膜瘤的单细胞转录组直接比较表明，SFT细胞中内皮标志物的表达富集，而脑膜瘤细胞中壁细胞标志物的表达富集。脑膜SFT空间转录组在世界卫生组织组织学分级以及患者匹配的原发/复发或颅内/转移样本对中，显示出细胞状态、基因表达程序和细胞间相互作用方面区域特异性的肿瘤内异质性。
这些结果揭示了与其他中枢神经系统肿瘤相比脑膜SFT生物学的潜在途径，并为整合人类癌症和正常组织中的单细胞、空间和批量RNA测序数据提供了框架。
