SCI-Atlas
A single-cell spatial atlas of spinal cord injury in mouse and human
Spinal cord injury starts a dynamic cascade of multicellular events. These events end in intractable pathology and scar formation. To define the spatial and temporal organisation of these processes, we built a cross-species atlas of spinal cord injury at single-cell spatial resolution.
We integrated mouse single-cell and single-nucleus RNA-sequencing datasets with spatial transcriptomic profiling. We then performed single-cell spatial mapping of mouse and human spinal cord injury across acute, subacute, and chronic stages. The resulting atlas resolves injury-associated cell states within evolving tissue microenvironments.
In the mouse, we identified an early interferon-responsive astrocyte border that precedes canonical reactive astrogliosis, a metabolically stratified myeloid architecture around the lesion core, and an ordered transition between inflammatory and meningeal-stromal microenvironments. In human post-mortem tissue, we resolved conserved and pathology-specific white-matter, lesion-border, epicentre, and stromal compartments, together with distinct injury-associated glial and fibroblast states.
The single-cell and spatial transcriptomics datasets can be interactively navigated and downloaded on this portal.
Publication
Spinal cord injury atlas at single-cell spatial resolution in mice and humans (in preparation)
Burnside ER*, Demirci Y*, Rademaker K*, Jin L, Lu C, Kazu Siqueira R, Roberts K, Tuck E, Katsirea Z, International Spinal Cord Injury Biobank, Stern S, Lee J, Saez-Rodriguez J, Tanevski J, Bradke F#, Bayraktar OA#.
*equal contribution ยท #corresponding authors
Correspondence: frank.bradke@dzne.de (F.B.), ob5@sanger.ac.uk (O.A.B.)
Preprint link comming soon!Datasets
Integrated single-cell atlas on CELLxGENE
167,493 cells from 6 integrated mouse sc/snRNA-seq datasets, spanning uninjured spinal cord and 1 to 90 days post injury. The atlas defines 18 coarse-grained cell types and 96 fine-grained cell states across neural, immune, vascular, and stromal populations.
Integrated reference atlas of mouse spinal cord injury.
Mouse Visium spatial data on WebAtlas
Transcriptome-wide Visium spatial profiling of sagittal spinal cord sections at 55 micron resolution. 20,431 spatial profiles across 12 sections, covering sham and 1, 3, 7, 14, and 28 days post injury, mapped to the integrated single-cell reference.
Coarse spatial map of spinal cord injury across time.
Mouse Xenium single-cell spatial on WebAtlas
Imaging-based single-cell spatial profiling with a targeted 480-gene Xenium panel. 478,231 segmented cells across 18 sections, covering sham and 1, 3, 7, 14, and 28 days post injury (n=3 animals per timepoint), with cell states transferred from the integrated atlas.
Single-cell resolved spatial architecture of mouse spinal cord injury.
Human Xenium single-cell spatial on WebAtlas
Single-cell spatial profiling of human post-mortem spinal cord with the 5,000-plex Xenium Prime panel. 854,165 cells across 12 transverse sections from 5 donors, spanning acute injury to 5.6 months post injury, resolving ten conserved and pathology-specific tissue microenvironments.
Single-cell resolved tissue microenvironments of human spinal cord injury.
Authors
Acknowledgements
We thank the human biospecimen donors and the International Spinal Cord Injury Biobank for providing samples. We thank the DZNE Animal Research Facility for mouse husbandry, and the Cellular Genomics Wet Lab support for technical assistance.
Participating institutions: German Center for Neurodegenerative Diseases (DZNE Bonn), Wellcome Sanger Institute, Heidelberg University and Heidelberg University Hospital, EMBL-EBI, ICORD (Vancouver), and UCL Cancer Institute.