Cell atlas of the developing human meninges reveals a dura-like nature of meningiomas

Abstract The vertebrate central nervous system is enveloped by the meninges, consisting of the pia, arachnoid and dura layers. The arachnoid is hypothesized to give rise to the most common primary intracranial tumours, meningiomas. However, supporting molecular evidence is lacking. There are no effective medical therapies to treat meningiomas that are resistant to local interventions, encumbered by our limited understanding of their cellular origin. Here, to advance our understanding of meningioma biology, we generated a comprehensive reference single-cell and spatial transcriptomic atlas of human fetal meninges at postconceptional weeks 5–13. We found that the meningeal layers develop concurrently, and identified an inner CDH1 -positive dura layer expressing tight-junction genes consistent with barrier function. Comparing meningiomas with fetal meninges, we show that, transcriptionally, meningioma cells resemble dura-lineage cells, and that common meningioma driver genes were expressed in the dura lineage. This raises the hypothesis that meningiomas could originate from dura-lineage cells.