Profiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair

eLife

Rui Feng¹  Oshri Avraham¹  Eric Edward Ewan¹  Valeria Cavalli²  Guoyan Zhao³  Justin Rustenhoven⁴ 

[1] Department of Neuroscience, Washington University School of Medicine, Saint Louis, United States;Department of Neuroscience, Washington University School of Medicine, Saint Louis, United States;Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, United States;Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, United States;Department of Neuroscience, Washington University School of Medicine, Saint Louis, United States;Department of Pathology and Immunology, Washington University School of Medicine, St Louis, United States;Department of Pathology and Immunology, Washington University School of Medicine, St Louis, United States;Center for Brain Immunology and Glia (BIG), Washington University School of Medicine, St Louis, United States;

关键词: axon regeneration;    satellite glial cells;    nerve repair;    single-cell RNA sequencing;    dorsal root ganglion;    Mouse;   

DOI  :  10.7554/eLife.68457

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Sensory neurons with cell bodies in dorsal root ganglia (DRG) represent a useful model to study axon regeneration. Whereas regeneration and functional recovery occurs after peripheral nerve injury, spinal cord injury or dorsal root injury is not followed by regenerative outcomes. Regeneration of sensory axons in peripheral nerves is not entirely cell autonomous. Whether the DRG microenvironment influences the different regenerative capacities after injury to peripheral or central axons remains largely unknown. To answer this question, we performed a single-cell transcriptional profiling of mouse DRG in response to peripheral (sciatic nerve crush) and central axon injuries (dorsal root crush and spinal cord injury). Each cell type responded differently to the three types of injuries. All injuries increased the proportion of a cell type that shares features of both immune cells and glial cells. A distinct subset of satellite glial cells (SGC) appeared specifically in response to peripheral nerve injury. Activation of the PPARα signaling pathway in SGC, which promotes axon regeneration after peripheral nerve injury, failed to occur after central axon injuries. Treatment with the FDA-approved PPARα agonist fenofibrate increased axon regeneration after dorsal root injury. This study provides a map of the distinct DRG microenvironment responses to peripheral and central injuries at the single-cell level and highlights that manipulating non-neuronal cells could lead to avenues to promote functional recovery after CNS injuries or disease.

【 授权许可】

CC BY