Satellite glial cells promote regenerative growth in sensory neurons

Nat Commun. 2020 Sep 29;11(1):4891. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology
  • Cell Proliferation
  • Fatty Acid Synthases / genetics
  • Fatty Acid Synthases / metabolism
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Regeneration*
  • Neuroglia / cytology*
  • Neuroglia / metabolism
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • Peripheral Nerve Injuries / genetics
  • Peripheral Nerve Injuries / metabolism
  • Peripheral Nerve Injuries / physiopathology
  • Peripheral Nerves / growth & development
  • Peripheral Nerves / metabolism
  • Peripheral Nerves / physiopathology
  • Sensory Receptor Cells / cytology*
  • Sensory Receptor Cells / metabolism
  • Signal Transduction

Substances

  • PPAR alpha
  • Fatty Acid Synthases