Current evidence on the cell of origin of meningiomas disputes the arachnoid cap cell dogma

Abstract

Background For over a century, the dominant hypothesis has maintained that meningiomas arise exclusively from arachnoid cap cells. However, emerging evidence from single-cell transcriptomics, spatial sequencing, developmental biology, and transgenic animal models suggests a significantly more complex and heterogeneous cellular origin. Methods This mini-review revisits historical perspectives and critically evaluates the limitations of the traditional arachnoidbased paradigm. By synthesizing classical histological insights with contemporary molecular and proteomic data, the study explores alternative hypotheses, particularly those implicating fibroblast-like or regionally distinct meningeal progenitors. Results The synthesis of multi-omic and developmental data indicates that a singular cellular source is insufficient to account for the clinical and biological diversity of meningiomas. Findings suggest that meningioma ontogeny is likely driven by a broader spectrum of progenitors whose characteristics vary according to anatomical location and embryological lineage. Conclusions A redefinition of meningioma ontogeny is necessary. Future classification and therapeutic strategies should reflect the inherent diversity of their cellular sources and anatomical environments, moving beyond the classical arachnoidcap-cell model.