Satellite glial cells promote regenerative growth in sensory neurons

Oshri Avraham,Pan-Yue Deng,Rejji Kuruvilla,Clay F Semenkovich,Sara Jones,Vitaly A Klyachko,Valeria Cavalli

doi:10.1038/s41467-020-18642-y

Abstract

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.

Highlights

Peripheral sensory neurons regenerate their axon after nerve injury to enable functional recovery
satellite glial cells (SGC) have been identified mostly based on their morphology and location
In this study, using single cell RNA-seq, we reveal that nerve injury alters the gene expression profile in SGC, which is mostly related to lipid metabolism, including fatty acid synthesis and PPARα signaling

Summary

Introduction

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. 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. 1234567890():,; Unlike neurons in the central nervous system (CNS), peripheral sensory neurons with cell soma in dorsal root ganglia (DRG) switch to a regenerative state after nerve injury to enable axon regeneration and functional recovery. Several SGC markers have been characterized, including the inwardly rectifying potassium channel (Kir4.1)[8], cadherin 199, the calcium activated potassium channel (SK3)[10,11], and glutamine synthetase (GS)[5,12]

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Conclusion