Dissecting the Endothelial Cell Landscape in Meningioma: Single-Cell Insights into PLVAP+ Subpopulations and Their Role in Tumor Angiogenesis

Liang Zhao¹Hongling Jia^2*Zhikai Xiahou³Li Ren¹Yanbing Song¹Hao Xu¹Zhihan Wang¹Jin Xing^1*

• ¹Department of Neurosurgery, Shanghai Pudong Hospital, Fudan University, Shanghai, Shanghai Municipality, China
• ²First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
• ³China Institute of Sport and Health Science, Beijing Sport University, Beijing, China

Background: Meningioma (MEN) is one of the most common intracranial tumors, with a significantly higher incidence rate in females than in males. Although the majority of cases are benign, tumors located in complex anatomical regions or classified as atypical or malignant have a high recurrence rate, underscoring the need to optimize therapeutic strategies to improve patient outcomes. Therefore, this study utilizes single-cell RNA-sequencing technology to investigate the interaction mechanisms between endothelial cells (ECs) and meningiomas, aiming to identify potential therapeutic targets for the treatment of MEN patients.Methods:Tissue origin analysis of different EC subpopulations was performed using Ro/e preference analysis. Gene Ontology and Gene Set Enrichment Analysis were employed to enrich and identify relevant biological processes. Slingshot and CytoTRACE were used to determine the differentiation trajectories of cell subpopulations. CellChat was utilized to predict intercellular communication between EC subpopulations and meningioma cells (MGCs). The transcription factor (TF) networks of EC subpopulations were constructed using pySCENIC, and the function of ETS1 was validated in vitro experiments.Results:The MEN and temporal lobe tissues’ datasets were processed through quality control and screening, and dimensionality reduction clustering identified eight cell types. We found that ECs might play a role in MEN progression and further classified them into four subpopulations. Among these, the C2 PLVAP+ ECs were predominantly located at the later stages of differentiation in the Slingshot analysis, suggesting a critical role in MEN’s development. Cell communication analysis revealed that MGCs might stimulate ECs to secrete angiopoietin via the MDK-NCL ligand-receptor pair, promoting angiogenesis and MEN’s progression. Using pySCENIC analysis, the key TF ETS1 was identified. In vitro experiments demonstrated that ETS1 promoted ECs angiogenesis, proliferation, and migration, providing valuable insights for clinical strategies targeting MEN’s treatment.Conclusion:We identified a key ECs subpopulation, C2 PLVAP+ ECs, which was at a critical stage of MEN progression and might influence MEN development through the MK signaling pathway via the MDK-NCL ligand-receptor pair. Additionally, we discovered the critical TF ETS1 and validated through in vitro experiments that it promoted MEN’s progression, offering a new perspective for clinical treatment strategies.