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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Autores principales: Oshri Avraham, Rui Feng, Eric Edward Ewan, Justin Rustenhoven, Guoyan Zhao, Valeria Cavalli
Formato: article
Lenguaje:EN
Publicado: eLife Sciences Publications Ltd 2021
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Acceso en línea:https://doaj.org/article/5442f1c8cdd94e88a642340c71c4afe2
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic axon regeneration
satellite glial cells
nerve repair
single-cell RNA sequencing
dorsal root ganglion
Medicine
R
Science
Q
Biology (General)
QH301-705.5
spellingShingle 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
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AT ruifeng profilingsensoryneuronmicroenvironmentafterperipheralandcentralaxoninjuryrevealskeypathwaysforneuralrepair
AT ericedwardewan profilingsensoryneuronmicroenvironmentafterperipheralandcentralaxoninjuryrevealskeypathwaysforneuralrepair
AT justinrustenhoven profilingsensoryneuronmicroenvironmentafterperipheralandcentralaxoninjuryrevealskeypathwaysforneuralrepair
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