@article{15c20e00a1804652a33a19e2e877f2ed,
title = "Profiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair",
abstract = "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.",
author = "Oshri Avraham and Rui Feng and Ewan, {Eric Edward} and Justin Rustenhoven and Guoyan Zhao and Valeria Cavalli",
note = "Funding Information: We thank members of the Cavalli lab for valuable discussions. We thank Mayssa Mokalled for helpful discussion and comments on glial cells and spinal cord injury. We thank Jonathan Kipnis for constructive discussions and precious help with flow cytometry. We thank Harrison Gabel for his generous gift of the Baf53b-cre mouse line and Joseph Dougherty for providing the Aldh1l1::Rpl10a-Egfp transgenic line. We gratefully acknowledge Greg Strout, Ross Kossina and Dr. James Fitzpatrick from the Washington University Center for Cellular Imaging (WUCCI), which is supported in part by Washington University School of Medicine, The Children{\textquoteright}s Discovery Institute of Washington University, and St. Louis Children{\textquoteright}s Hospital (CDI-CORE-2015–505 and CDI-CORE-2019–813) and the Foundation for Barnes-Jewish Hospital (3770) for assistance in acquiring and interpreting Transmission Electron Microscopy (TEM) data. We thank the Bioinformatics Research Core for CellPhone DB analysis. We also thank Anushree Seth and Madison Mack in association with InPrint for illustration in Figure 1d. This work was funded in part by a post-doctoral fellowship from The McDonnell Center for Cellular and Molecular Neurobiology to OA, by The McDonnell Center for Cellular and Molecular Neurobiology, NIH grant R35 NS122260, R01 NS111719 and R21 NS115492 to V.C. Publisher Copyright: {\textcopyright} 2021, eLife Sciences Publications Ltd. All rights reserved.",
year = "2021",
month = sep,
doi = "10.7554/eLife.68457",
language = "English",
volume = "10",
journal = "eLife",
issn = "2050-084X",
}