Novel Human Meningioma Organoids Recapitulate the Aggressiveness of the Initiating Cell Subpopulations Identified by ScRNA-Seq

High-grade meningioma has an unsatisfactory outcome despite surgery and postoperative radiotherapy; however, the factors driving its malignancy and recurrence remain largely unknown, which limits the development of systemic treatments. Single-cell RNA sequencing (scRNA-Seq) technology is a powerful tool for studying intratumoral cellular heterogeneity and revealing the roles of various cell types in oncogenesis. In this study, scRNA-Seq is used to identify a unique initiating cell subpopulation (SULT1E1(+)) in high-grade meningiomas. This subpopulation modulates the polarization of M2-type macrophages and promotes meningioma progression and recurrence. A novel patient-derived meningioma organoid (MO) model is established to characterize this unique subpopulation. The resulting MOs fully retain the aggressiveness of SULT1E1(+) and exhibit invasiveness in the brain after orthotopic transplantation. By targeting SULT1E1(+) in MOs, the synthetic compound SRT1720 is identified as a potential agent for systemic treatment and radiation sensitization. These findings shed light on the mechanism underlying the malignancy of high-grade meningiomas and provide a novel therapeutic target for refractory high-grade meningioma.

Automated summary

High-grade meningioma has a limited response to surgery and postoperative radiotherapy, and the factors that drive its malignancy and recurrence are largely unknown. This study used scRNA-Seq to identify a unique initiating cell subpopulation (SULT1E1(+)) in high-grade meningiomas, and found that it modulates the polarization of M2-type macrophages, promoting meningioma progression and recurrence. A novel patient-derived meningioma organoid (MO) model was also established, which fully retained the aggressiveness of SULT1E1(+) and showed invasiveness in the brain after orthotopic transplantation. Targeting SULT1E1(+) in MOs identified the synthetic compound SRT1720 as a potential agent for systemic treatment and radiation sensitization.