Transcriptional reprogramming of distinct peripheral sensory neuron subtypes after axonal injury

Lite Yang, M.S.
Department of Neurology
Division of Basic Neuroscience Research
Poster Overview

Primary somatosensory neurons are specialized to detect and transmit sensory information such as touch or temperature. They differ in cell size, myelination, and the gene expression, which together define their diverse transcriptional and functional identity. By profiling sensory ganglia at single-cell resolution, we identified nine major somatosensory neuronal subtypes, and find that all neuronal subtypes undergo a similar transcriptional response after they are physically injured. This event is not observed in non-neuronal cells. This change in gene expression promotes axonal regeneration and suppresses cell identity. Once axonal regeneration is completed and injury is recovered, the original cell identity is restored.

Scientific Abstract

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.

Clinical Implications
Our study identified genes selectively expressed in primary somatosensory neuronal subtypes, as well as genes induced in each subtype after injury. These findings may guide the development of more selective next-generation pain therapeutics.
Research Areas
Authors
William Renthal, Ivan Tochitsky, Lite Yang, Yung-Chih Cheng, Emmy Li, Riki Kawaguchi, Daniel H. Geschwind, Clifford J. Woolf
Principal Investigator
William Renthal

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