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Transcriptional Reprogramming of Distinct Peripheral Sensory Neuron Subtypes after Axonal Injury

Neuron (Cambridge, Mass.), 2020-10, Vol.108 (1), p.128-144.e9 [Peer Reviewed Journal]

2020 Elsevier Inc. ;Copyright © 2020 Elsevier Inc. All rights reserved. ;COPYRIGHT 2020 Elsevier B.V. ;2020. Elsevier Inc. ;ISSN: 0896-6273 ;EISSN: 1097-4199 ;DOI: 10.1016/j.neuron.2020.07.026 ;PMID: 32810432

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Title:
Transcriptional Reprogramming of Distinct Peripheral Sensory Neuron Subtypes after Axonal Injury
Author: Renthal, William ; Tochitsky, Ivan ; Yang, Lite ; Cheng, Yung-Chih ; Li, Emmy ; Kawaguchi, Riki ; Geschwind, Daniel H. ; Woolf, Clifford J.
Subjects: Activating transcription factor 3 ; Activating Transcription Factor 3 - genetics ; Animals ; ATF3 ; axon growth ; Axons ; Axotomy ; cell identity ; Cell size ; Cellular Reprogramming - genetics ; Crush Injuries - genetics ; Crush Injuries - metabolism ; Diabetic neuropathy ; dorsal root ganglion ; Fibroblasts ; Ganglia, Spinal - cytology ; Gene expression ; Gene Expression Regulation - genetics ; Genes ; Genetic aspects ; Genetic transcription ; Ion channels ; Lumbar Vertebrae ; Mechanoreceptors - metabolism ; Medical colleges ; Mice ; Myelination ; nerve injury ; Nerve Regeneration ; Neuralgia - genetics ; Neuronal Plasticity - genetics ; Neurons ; Neurophysiology ; Nociceptors - metabolism ; Pain ; Peripheral Nerve Injuries - genetics ; Peripheral nerves ; Recovery of Function ; Regeneration ; Reinnervation ; reprogramming ; RNA ; RNA-Seq ; Sciatic Nerve - injuries ; Sciatic Nerve - surgery ; Sensory evaluation ; sensory neuron ; Sensory neurons ; Sensory Receptor Cells - metabolism ; Single-Cell Analysis ; single-cell RNA-seq ; Spinal Nerves - injuries ; Spinal Nerves - surgery ; Transcription factors ; Transcriptome
Is Part Of: Neuron (Cambridge, Mass.), 2020-10, Vol.108 (1), p.128-144.e9
Description: 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. •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 Dorsal root ganglion neurons transduce somatosensory and painful stimuli in the peripheral nervous system. Renthal et al. characterize a transcriptional program induced across neuronal subtypes after peripheral nerve injury that is necessary for nerve regeneration.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 0896-6273
EISSN: 1097-4199
DOI: 10.1016/j.neuron.2020.07.026
PMID: 32810432
Source: MEDLINE
Open Access: Cell Press Free Archives

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Transcriptional Reprogramming of Distinct Peripheral Sensory Neuron Subtypes after Axonal Injury

2020 Elsevier Inc. ;Copyright © 2020 Elsevier Inc. All rights reserved. ;COPYRIGHT 2020 Elsevier B.V. ;2020. Elsevier Inc. ;ISSN: 0896-6273 ;EISSN: 1097-4199 ;DOI: 10.1016/j.neuron.2020.07.026 ;PMID: 32810432

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