Spatially resolved multiomics of human meningeal development reveal lineage and disease dynamics.

Abstract:: The meninges are increasingly recognized as key stromal and immune niches supporting cranial development. Here we constructed a paired single-nuclei RNA and Assay for Transposase-Accessible Chromatin atlas of human meningeal development from 6 to 21 postconception weeks across cranial regions. By integrating spatial transcriptomics, we resolved cell types across meningeal layers. Our multiomic atlas defines gene regulatory networks underlying blood-brain barrier endothelial identity during development. Within immune compartments, the data support a yolk sac origin for meningeal myeloid lineages, including perivascular macrophages primed for barrier immunity. We present two analytical tools: Nichefinder, for spatial label transfer and proximity analysis, and cell2home, for inferring chemotactic signalling. Using cell2home, we identify interactions potentially driving B cell migration from cranial marrow into prenatal meninges. We studied trisomy 21, and observed reduced fibroblast chemokine expression with enhanced JAK-STAT signalling. Together, this work provides a developmental atlas of the human meninges and defines cellular and regulatory programs shaping early barrier immunity.

Authors:: K To, JP Pett, O Dufva, N-J Chipampe, K Polanski, A-M Cujba, K Roberts, AV Predeus, N Yayon, K Kanemaru, MI Patel, D Horsfall, T Li, P Mazin, B Cakir, R Kapuge, A Wilk, F Memi, X He, N Solanky, S Kayhanian, R Mair, K Rademaker, OA Bayraktar, M Haniffa, RA Barker, CD Buckley, SA Teichmann

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