Resources
Authors & Affiliations
Nicola Regazzi, Claudia Kathe, Thomas H. Hutson, Matthieu Gautier, Alan Y. Teo, Katia Galan, Simon Borgognon, Charles F. V. Latchoumane, Sandra Braz, Joana Nogueira-Rodrigues, Jeff M. Gidday, Matthew Lawrence, Monica M. Sousa, Quentin Barraud, Mark A. Anderson, Michael Skinnider, Jocelyne Bloch, Grégoire Courtine, Jordan Squair
Abstract
A spinal cord injury (SCI) triggers a multifaceted series of secondary injuries, involving inflammation, cell death, demyelination, and scar formation. How the individual types and subtypes of cells of the central nervous system coordinate to mediate this response remains unclear. While much of our current knowledge is derived from rodents, therapies effective in these models have not translated successfully to clinical trials. Understanding molecular responses across species—lower vertebrates, non-primate mammals, and primates—is crucial for formulating effective human treatments. We aim to utilize single-nucleus RNA-sequencing (snRNA-seq) to develop a comprehensive atlas of cell-specific, time-dependent molecular responses to various SCI severities in mice, rats, zebrafish, spiny mice, neonatal mice, and non-human primate models. Complemented by kinematic recordings and histological validations, this atlas will elucidate spontaneous regeneration capabilities in different species. By comparing molecular signatures across species, we can uncover biological disparities hindering translation of preclinical therapies and identify targets for regeneration mechanisms. This cross-species molecular atlas of SCI promises to enhance our understanding of SCI pathogenesis and accelerate the development of effective therapies.