Single-cell and spatial atlases of spinal cord injury in the Tabulae Paralytica.
Details
Serval ID
serval:BIB_1C539D189A0B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Single-cell and spatial atlases of spinal cord injury in the Tabulae Paralytica.
Journal
Nature
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Publication state
Published
Issued date
07/2024
Peer-reviewed
Oui
Volume
631
Number
8019
Pages
150-163
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
Here, we introduce the Tabulae Paralytica-a compilation of four atlases of spinal cord injury (SCI) comprising a single-nucleus transcriptome atlas of half a million cells, a multiome atlas pairing transcriptomic and epigenomic measurements within the same nuclei, and two spatial transcriptomic atlases of the injured spinal cord spanning four spatial and temporal dimensions. We integrated these atlases into a common framework to dissect the molecular logic that governs the responses to injury within the spinal cord <sup>1</sup> . The Tabulae Paralytica uncovered new biological principles that dictate the consequences of SCI, including conserved and divergent neuronal responses to injury; the priming of specific neuronal subpopulations to upregulate circuit-reorganizing programs after injury; an inverse relationship between neuronal stress responses and the activation of circuit reorganization programs; the necessity of re-establishing a tripartite neuroprotective barrier between immune-privileged and extra-neural environments after SCI and a failure to form this barrier in old mice. We leveraged the Tabulae Paralytica to develop a rejuvenative gene therapy that re-established this tripartite barrier, and restored the natural recovery of walking after paralysis in old mice. The Tabulae Paralytica provides a window into the pathobiology of SCI, while establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine.
Keywords
Animals, Female, Male, Mice, Atlases as Topic, Cell Nucleus/metabolism, Epigenomics, Neurons/pathology, Neurons/metabolism, Paralysis/genetics, Paralysis/pathology, Paralysis/rehabilitation, Paralysis/therapy, Recovery of Function, Single-Cell Analysis, Spinal Cord/pathology, Spinal Cord Injuries/genetics, Spinal Cord Injuries/pathology, Spinal Cord Injuries/rehabilitation, Spinal Cord Injuries/therapy, Transcriptome, Walking, Anatomy, Artistic, Multiomics, Neural Pathways, Genetic Therapy
Pubmed
Web of science
Create date
21/06/2024 10:07
Last modification date
27/07/2024 7:00