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.

SCI-Atlas overview: integrated single-cell and spatial transcriptomic atlas of spinal cord injury

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

EB

Emily R Burnside

Co-first author

DZNE Bonn

YD

Yeliz Demirci

Co-first author

Wellcome Sanger Institute

KR

Koen Rademaker

Co-first author

Wellcome Sanger Institute

LJ

Liying Jin

Author

Wellcome Sanger Institute

CL

Chang Lu

Author

Heidelberg University

RK

Rodrigo Kazu Siqueira

Author

Wellcome Sanger Institute

KR

Kenny Roberts

Author

Wellcome Sanger Institute

ET

Elizabeth Tuck

Author

Wellcome Sanger Institute

ZK

Zoi Katsirea

Author

Wellcome Sanger Institute

SS

Sina Stern

Author

DZNE Bonn

JL

Jimmy Lee

Author

Wellcome Sanger Institute

JS

Julio Saez-Rodriguez

Author

Heidelberg University / EMBL-EBI

JT

Jovan Tanevski

Author

Heidelberg University

FB

Frank Bradke

Co-principal investigator

DZNE Bonn

OB

Omer Ali Bayraktar

Co-principal investigator

Wellcome Sanger Institute / UCL

SB

International Spinal Cord Injury Biobank

Human biospecimens

ICORD, Vancouver


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.