RESUMO
Axon regeneration can be induced across anatomically complete spinal cord injury (SCI), but robust functional restoration has been elusive. Whether restoring neurological functions requires directed regeneration of axons from specific neuronal subpopulations to their natural target regions remains unclear. To address this question, we applied projection-specific and comparative single-nucleus RNA sequencing to identify neuronal subpopulations that restore walking after incomplete SCI. We show that chemoattracting and guiding the transected axons of these neurons to their natural target region led to substantial recovery of walking after complete SCI in mice, whereas regeneration of axons simply across the lesion had no effect. Thus, reestablishing the natural projections of characterized neurons forms an essential part of axon regeneration strategies aimed at restoring lost neurological functions.
Assuntos
Axônios , Regeneração Nervosa , Paralisia , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Caminhada , Animais , Camundongos , Axônios/fisiologia , Regeneração Nervosa/genética , Regeneração Nervosa/fisiologia , Neurônios/fisiologia , Paralisia/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , ConectomaRESUMO
We present Augur, a method to prioritize the cell types most responsive to biological perturbations in single-cell data. Augur employs a machine-learning framework to quantify the separability of perturbed and unperturbed cells within a high-dimensional space. We validate our method on single-cell RNA sequencing, chromatin accessibility and imaging transcriptomics datasets, and show that Augur outperforms existing methods based on differential gene expression. Augur identified the neural circuits restoring locomotion in mice following spinal cord neurostimulation.