TY - JOUR
T1 - Satellite glial cells promote regenerative growth in sensory neurons
AU - Avraham, Oshri
AU - Deng, Pan Yue
AU - Jones, Sara
AU - Kuruvilla, Rejji
AU - Semenkovich, Clay F.
AU - Klyachko, Vitaly A.
AU - Cavalli, Valeria
N1 - Funding Information:
We would like to thank members of the Cavalli lab for valuable discussions. We would like to thank the following investigators for their generous gifts of mouse lines: Dr. Toshihiko Hosoya for the BLBP-cre ER mice, Dr. Yuji Oawada for the Fabp7KO mice, and Dr. Harrison Gabel for the Sun1GFP mice. 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’s Discovery Institute of Washington University, and St. Louis Children’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 also thank Anushree Seth and Madison Mack in association with InPrint for illustration in Fig. 1a. This work was funded in part by a postdoctoral fellowship from The McDonnell Center for Cellular and Molecular Neurobiology to O.A., by NIH grant NS111596 to V.A.K., and by The McDonnell Center for Cellular and Molecular Neurobiology and NIH grant NS111719 to V.C.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Peripheral sensory neurons regenerate their axon after nerve injury to enable functional recovery. Intrinsic mechanisms operating in sensory neurons are known to regulate nerve repair, but whether satellite glial cells (SGC), which completely envelop the neuronal soma, contribute to nerve regeneration remains unexplored. Using a single cell RNAseq approach, we reveal that SGC are distinct from Schwann cells and share similarities with astrocytes. Nerve injury elicits changes in the expression of genes related to fatty acid synthesis and peroxisome proliferator-activated receptor (PPARα) signaling. Conditional deletion of fatty acid synthase (Fasn) in SGC impairs axon regeneration. The PPARα agonist fenofibrate rescues the impaired axon regeneration in mice lacking Fasn in SGC. These results indicate that PPARα activity downstream of FASN in SGC contributes to promote axon regeneration in adult peripheral nerves and highlight that the sensory neuron and its surrounding glial coat form a functional unit that orchestrates nerve repair.
AB - Peripheral sensory neurons regenerate their axon after nerve injury to enable functional recovery. Intrinsic mechanisms operating in sensory neurons are known to regulate nerve repair, but whether satellite glial cells (SGC), which completely envelop the neuronal soma, contribute to nerve regeneration remains unexplored. Using a single cell RNAseq approach, we reveal that SGC are distinct from Schwann cells and share similarities with astrocytes. Nerve injury elicits changes in the expression of genes related to fatty acid synthesis and peroxisome proliferator-activated receptor (PPARα) signaling. Conditional deletion of fatty acid synthase (Fasn) in SGC impairs axon regeneration. The PPARα agonist fenofibrate rescues the impaired axon regeneration in mice lacking Fasn in SGC. These results indicate that PPARα activity downstream of FASN in SGC contributes to promote axon regeneration in adult peripheral nerves and highlight that the sensory neuron and its surrounding glial coat form a functional unit that orchestrates nerve repair.
UR - http://www.scopus.com/inward/record.url?scp=85091718832&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-18642-y
DO - 10.1038/s41467-020-18642-y
M3 - Article
C2 - 32994417
AN - SCOPUS:85091718832
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4891
ER -