SUPR
Cellular arrangements driving locomotor recovery after spinal cord injury
Dnr:

NAISS 2024/23-580

Type:

NAISS Small Storage

Principal Investigator:

Alberto Joven Araus

Affiliation:

Karolinska Institutet

Start Date:

2024-11-12

End Date:

2025-11-01

Primary Classification:

10610: Bioinformatics and Systems Biology (methods development to be 10203)

Allocation

Abstract

Spinal cord trauma causes an irreversible loss of motor control in most four-legged vertebrates. Remarkably, newts recover swimming and walking just few weeks after full transection, by regenerating central nervous tissue through mechanisms that are not fully understood. We are exploring potential mechanisms behind the functional recovery observed in newts. Using machine learning and MRI, we dissected the newt locomotor behaviors and longitudinally follow the recovery of spinal cord tissue, to select key time points of tissue regeneration linked to functional recovery. We performed single nuclei RNAseq and Spatial transcriptome analysis with subcellular resolution at key moments along the regeneration process. Our ongoing analyses of both data sets allow us to uncover multiple cellular and molecular mechanisms potentially deployed in the functional regeneration of CNS, including immune cell activation, neural stem cell proliferation, neurogenesis and axonogenesis. To conclude, we are using transgenic newts, AAVs and lineage tracing to confirm that cell proliferation, migration and signalling are key processes carried by specific cell types in spatially and temporally defined windows. Our study provides a new foundation of knowledge, setting the basis for future studies on fundamental cellular processes along the course of spinal cord regeneration.