Meningeal solitary fibrous tumor cell states phenocopy cerebral vascular development and homeostasis.
Publication Year:
2025
PubMed ID:
39207122
Public Summary:
Solitary fibrous tumors (SFTs) are rare tumors that can develop in the tissues surrounding the brain and spinal cord. Although they can often be treated with surgery, some tumors return or spread to other parts of the body. Little is known about the different types of tumor cells within SFTs or the biological processes that contribute to their behavior.
In this study, we used advanced technologies that measure gene activity in individual cells and across different regions of tumors to create a detailed map of meningeal SFTs. We found that these tumors contain diverse populations of cells organized into distinct regions, with many tumor cells resembling cells involved in the development and maintenance of blood vessels in the brain. These cellular states appear to be flexible, suggesting that tumor cells can transition between different biological programs. We also identified extensive communication between tumor cells and surrounding cells, particularly blood vessel cells and developing neural cells. Importantly, these patterns varied across different tumor grades and between tumors that had recurred or spread to other parts of the body.
Together, our findings provide a new view of the cellular organization and biology of meningeal SFTs. Understanding how these tumor cells change, interact with neighboring cells, and differ across regions of the same tumor may ultimately help identify biological features associated with tumor recurrence or spread and provide new directions for developing more effective treatments.
Scientific Abstract:
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.