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
- Ana-Maria Cujba (ORCID: https://orcid.org/0000-0003-3917-6751)
- Omer Ali Bayraktar (ORCID: https://orcid.org/0000-0001-6055-277X)
- Kazumasa Kanemaru (ORCID: https://orcid.org/0000-0003-0018-8966)
- Sarah Amalia Teichmann (ORCID: https://orcid.org/0000-0002-6294-6366)
- J. Patrick Pett (ORCID: https://orcid.org/0000-0002-5249-444X)
- Kenny S. Roberts (ORCID: https://orcid.org/0000-0001-6155-0821)
- Alexander V. Predeus (ORCID: https://orcid.org/0000-0002-2750-1599)
- Batuhan Çakır (ORCID: https://orcid.org/0000-0003-4513-606X)
- Christopher Dominic Buckley (ORCID: https://orcid.org/0000-0001-6924-6402)
- Manal Patel (ORCID: https://orcid.org/0000-0001-7438-2468)
- Muzlifah A. Haniffa (ORCID: https://orcid.org/0000-0002-3927-2084)
- Xiaoling He (ORCID: https://orcid.org/0009-0004-1002-8418)
- Nadav Yayon (ORCID: https://orcid.org/0000-0002-7034-0524)
- Koen Rademaker (ORCID: https://orcid.org/0000-0003-3059-5183)
- Roger A. Barker (ORCID: https://orcid.org/0000-0001-8843-7730)
- Richard James Mair (ORCID: https://orcid.org/0000-0001-8235-5689)
- Dave Horsfall (ORCID: https://orcid.org/0000-0002-8086-812X)
- Nana-Jane Chipampe (ORCID: https://orcid.org/0000-0002-8802-0473)
- Krzysztof Polański (ORCID: https://orcid.org/0000-0002-2586-9576)
- Kendrick To (ORCID: https://orcid.org/0000-0001-9262-7190)
- Pavel Mazin
- Olli Dufva (ORCID: https://orcid.org/0000-0002-8084-0282)
- Fani Memi
- Rakesh Kapuge
- Nita Solanky
- Alicja Wilk
- Tong Li
- Saeed Kayhanian
Institutions
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- University of Cambridge (GB)
- Cancer Research UK (GB)
- Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
- Cambridge University Hospitals NHS Foundation Trust (GB)
- Wellcome Sanger Institute (GB)
- University of Oxford (GB)
- Cancer Research UK Cambridge Center (GB)
- NIHR Newcastle Biomedical Research Centre (GB)
- Kennedy Institute of Rheumatology (GB)
- University College London (GB)
- Newcastle University (GB)
Publication Details
- Journal
- Nature Cell Biology
- Published
- 2026-09-28
- DOI
- https://doi.org/10.1038/s41556-026-02075-8
- Citations
- 1
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 2.44