EPCO-48. THE SINGLE-CELL AND SPATIAL TRANSCRIPTOMIC ARCHITECTURE OF MENINGEAL SOLITARY FIBROUS TUMORS PHENOCOPIES CEREBRAL VASCULAR DEVELOPMENT AND HOMEOSTASIS

Abstract INTRODUCTION Meningeal solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that are associated with local recurrence and distant metastasis. The cell states and spatial transcriptomic architecture of SFTs are unknown. METHODS Single-cell RNA sequencing or spatial transcriptomic sequencing were performed on 40,022 cells or 23,682 spatial transcriptomes from 12 meningeal SFT samples. Datasets were corrected for batch effects using Harmony and integrated using uniform maniform approximation and projection (UMAP). Clusters were defined using automated cell type classification, cell signature gene sets, cell cycle analysis, and differentially expressed marker genes. Trajectory analyses were performed using RNA velocity and pseudotime. Cell-cell communication analysis was performed using CellChat. RESULTS were validated using immunofluorescence and immunohistochemistry and generalized using comparisons to 30,934 single-cell transcriptomes from 6 meningioma samples, 139,134 perinatal human brain vascular single-cell transcriptomes, 84,138 adult human brain vascular single-cell transcriptomes, and DNA methylation profiles from 8 SFT and 221 meningioma samples. RESULTS Unsupervised hierarchical clustering of DNA methylation profiles revealed molecular distinction of meningeal SFTs from meningiomas. Deconvolution of vascular single-cell types showed SFT cell clusters resembling perinatal or adult fibroblasts, perinatal mitotic endothelia, and adult venous or arterial endothelia. UMAP and trajectory analyses showed SFTs were comprised of 8 interchangeable tumor cell states that were associated with cell adhesion (VCAM1, NCAM2), cell stress (EGR1), cell signaling (NOTCH3), extracellular matrix remodeling (ECM) (ADAMTS6, PLCG2), or protein synthesis pathways (RPL27A, RPL37). Cell-cell communication analyses identified single-cell and spatial interactions between VCAM1- or NCAM2-expressing SFT cells and endothelia or immature neurons in the tumor microenvironment, respectively. Single-cell deconvolution demonstrated evolution of ECM and protein synthesis SFT cells in paired primary/recurrent samples, and evolution of ECM SFT cells and macrophages in paired primary/metastatic samples. CONCLUSIONS The single-cell and spatial transcriptomic architecture of meningeal SFT reveals dynamic cell states that phenocopy cerebral vascular development and homeostasis.