Longitudinal Evolution and Cellular Plasticity in Meningioma: Insights From Single-Cell Transcriptomics.

Meningiomas are the most common primary intracranial tumors and exhibit a broad spectrum of clinical behavior, ranging from indolent growth to repeated recurrence and aggressive progression. Over the past decade, genomic, epigenomic, bulk transcriptomic, and single-cell studies have refined meningioma classification and identified molecular features associated with recurrence risk. However, recurrence is increasingly recognized as a dynamic process shaped by tumor-intrinsic plasticity, subtype redistribution, treatment-related selection, and remodeling of the tumor microenvironment. Recent longitudinal single-nucleus RNA sequencing of matched primary and recurrent meningiomas has extended this framework by demonstrating enrichment of proliferative, DNA repair, and extracellular matrix programs in recurrent disease, together with multidirectional transcriptional trajectories rather than simple linear progression. These findings complement earlier methylation- and transcriptome-based risk models, as well as cross-sectional single-cell studies that have highlighted neoplastic heterogeneity, macrophage interactions, and immune-state diversity across meningioma grades. Among recurrence-associated genes,