P13.18.A MENINGIOMAP: A SINGLE-CELL ATLAS OF MENINGIOMA ECOSYSTEMS AND MICROENVIRONMENTAL NETWORKS

Abstract BACKGROUND Meningiomas are the most common primary intracranial tumors, yet their cellular diversity, tumor-stroma interactions, and the relationship between neoplastic and normal meningeal cells remain incompletely understood. While recent studies have provided valuable single-cell insights into specific tumor contexts, a unified atlas encompassing both meningioma and healthy meningeal tissue across patients and studies is lacking. MATERIAL AND METHODS We constructed MeningioMap, a comprehensive single-cell atlas by harmonizing three publicly available datasets with in-house single-cell RNA sequencing (scRNA-seq) of surgically resected meningiomas and matched adjacent meningeal tissue. The dataset encompasses over 300,000 high-quality cells from 40+ patients, spanning diverse tumor grades, anatomical locations, histopathological subtypes, and genders. Standardized preprocessing, robust batch correction, and integrative clustering pipelines were employed. Preliminary spatial transcriptomic analyses further validated key tumor-stromal interactions predicted from scRNA-seq profile. RESULTS Meningioma delineates a high-resolution taxonomy of malignant and non-malignant cell states within the meningioma ecosystem. We identified distinct malignant subpopulations characterized by specific copy number alterations, transcriptional programs, and clinical associations with tumor grade. Comparative analysis with matched meninges uncovered conserved meningeal lineages and unveiled tumor-specific reprogramming events. Spatial transcriptomics confirmed localized immune remodeling and stromal activation signatures at the tumor-meninges interface. Notably, we identified a novel transitional malignant-stromal phenotype enriched in invasive tumor fronts, suggesting a potential driver of recurrence and therapeutic resistance. CONCLUSION MeningioMap represents the most extensive single-cell resource for meningioma and meningeal research to date. Beyond offering a foundational reference for tumor heterogeneity and cellular dynamics, it provides critical insights into tumor-microenvironment crosstalk, informing future strategies for precision diagnostics, risk stratification, and targeted therapeutic development. An interactive, publicly accessible portal will facilitate broad scientific and clinical utility.