Neuron
Volume 108, Issue 1, 14 October 2020, Pages 128-144.e9
Journal home page for Neuron

NeuroResource
Transcriptional Reprogramming of Distinct Peripheral Sensory Neuron Subtypes after Axonal Injury

https://doi.org/10.1016/j.neuron.2020.07.026Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Nerve injury induces a common transcriptional program across DRG neuronal subtypes

  • Injured DRG neurons transiently lose their transcriptional identity while regenerating

  • Atf3 drives transcriptional reprogramming and regeneration of DRG neurons after injury

  • Nerve injury induces distinct transcriptional responses in non-neuronal DRG cell types

Summary

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

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

Cited by (0)

5

These authors contributed equally

6

Lead Contact