Profiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair
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 sen...
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:5442f1c8cdd94e88a642340c71c4afe22021-11-25T10:27:50ZProfiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair10.7554/eLife.684572050-084Xe68457https://doaj.org/article/5442f1c8cdd94e88a642340c71c4afe22021-09-01T00:00:00Zhttps://elifesciences.org/articles/68457https://doaj.org/toc/2050-084XSensory 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.Oshri AvrahamRui FengEric Edward EwanJustin RustenhovenGuoyan ZhaoValeria CavallieLife Sciences Publications Ltdarticleaxon regenerationsatellite glial cellsnerve repairsingle-cell RNA sequencingdorsal root ganglionMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
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axon regeneration satellite glial cells nerve repair single-cell RNA sequencing dorsal root ganglion Medicine R Science Q Biology (General) QH301-705.5 |
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axon regeneration satellite glial cells nerve repair single-cell RNA sequencing dorsal root ganglion Medicine R Science Q Biology (General) QH301-705.5 Oshri Avraham Rui Feng Eric Edward Ewan Justin Rustenhoven Guoyan Zhao Valeria Cavalli Profiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair |
description |
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. |
format |
article |
author |
Oshri Avraham Rui Feng Eric Edward Ewan Justin Rustenhoven Guoyan Zhao Valeria Cavalli |
author_facet |
Oshri Avraham Rui Feng Eric Edward Ewan Justin Rustenhoven Guoyan Zhao Valeria Cavalli |
author_sort |
Oshri Avraham |
title |
Profiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair |
title_short |
Profiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair |
title_full |
Profiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair |
title_fullStr |
Profiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair |
title_full_unstemmed |
Profiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair |
title_sort |
profiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair |
publisher |
eLife Sciences Publications Ltd |
publishDate |
2021 |
url |
https://doaj.org/article/5442f1c8cdd94e88a642340c71c4afe2 |
work_keys_str_mv |
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