Meningeal solitary fibrous tumor cell states phenocopy cerebral vascular development and homeostasis

Meningeal solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that are associated with hematogenous metastasis, and the cell states and spatial transcriptomic architecture of SFTs are unknown. Here we use single-cell and spatial RNA sequencing to show SFTs are comprised of regionally distinct gene expression programs that resemble cerebral vascular development and homeostasis. Our results shed light on mechanisms underlying SFT biology in comparison to other central nervous system tumors and provide a framework for integrating single-cell and spatial transcriptomic data in human cancer samples. Genomic DNA underwent bisulfite conversion using the EZ DNA Methylation kit (Zymo Research, cat# D5004), followed by amplification, fragmentation, and hybridization to Infinium EPIC 850k Human DNA Methylation BeadChips (Illumina, cat# 20020530) according to manufacturer’s instructions at the Molecular Genomics Core at the University of Southern California (Los Angeles, CA). Bioinformatic analysis was performed in R (v4.2.1). DNA methylation data were preprocessed using the minifi pipeline (v1.47.0). In brief, probes were filtered and analyzed using normal-exponential out-of-band background correction, nonlinear dye bias correction, p-value with out-of-band array hybridization masking, and β value calculation (β=methylated/[methylated+unmethylated]). Principal component analysis was performed on the β methylation values from minfi pre-processing pipeline in R. Variable probes were identified from the first three principal components (PCs). PCs greater than 4 contributed to less than 5% of β value variance. The top 2000 probes were selected for analysis by ranking the absolute gene loading score values within PCs and the tumors were projected along the first two PCs.