Transcriptional Reprogramming of Distinct Peripheral Sensory Neuron Subtypes after Axonal Injury

Neuron. 2020 Oct 14;108(1):128-144.e9. doi: 10.1016/j.neuron.2020.07.026. Epub 2020 Aug 17.


Primary somatosensory neurons are specialized to transmit specific types of sensory information through differences in cell size, myelination, and the expression of distinct receptors and ion channels, which together define their transcriptional and functional identity. By profiling sensory ganglia at single-cell resolution, we find that all somatosensory neuronal subtypes undergo a similar transcriptional response to peripheral nerve injury that both promotes axonal regeneration and suppresses cell identity. This transcriptional reprogramming, which is not observed in non-neuronal cells, resolves over a similar time course as target reinnervation and is associated with the restoration of original cell identity. Injury-induced transcriptional reprogramming requires ATF3, a transcription factor that is induced rapidly after injury and necessary for axonal regeneration and functional recovery. Our findings suggest that transcription factors induced early after peripheral nerve injury confer the cellular plasticity required for sensory neurons to transform into a regenerative state.

Keywords: ATF3; axon growth; cell identity; dorsal root ganglion; gene expression; nerve injury; regeneration; reprogramming; sensory neuron; single-cell RNA-seq.

Publication types

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

MeSH terms

  • Activating Transcription Factor 3 / genetics*
  • Animals
  • Axons
  • Axotomy
  • Cellular Reprogramming / genetics*
  • Crush Injuries / genetics
  • Crush Injuries / metabolism
  • Ganglia, Spinal / cytology*
  • Gene Expression Regulation / genetics*
  • Lumbar Vertebrae
  • Mechanoreceptors / metabolism
  • Mice
  • Nerve Regeneration
  • Neuralgia / genetics*
  • Neuronal Plasticity / genetics
  • Nociceptors / metabolism
  • Peripheral Nerve Injuries / genetics*
  • RNA-Seq
  • Recovery of Function
  • Sciatic Nerve / injuries
  • Sciatic Nerve / surgery
  • Sensory Receptor Cells / metabolism*
  • Single-Cell Analysis
  • Spinal Nerves / injuries
  • Spinal Nerves / surgery
  • Transcriptome


  • Activating Transcription Factor 3
  • Atf3 protein, mouse