Sensory neurons display cell-type-specific vulnerability to loss of neuron-glia interactions

Peripheral nervous system (PNS) injuries initiate transcriptional changes in glial cells and sensory neurons that promote axonal regeneration. While the factors that initiate the transcriptional changes in glial cells are well characterized, the full range of stimuli that initiate the response of sensory neurons remain elusive. Here, using a genetic model of glial cell ablation, we find that glial cell loss results in transient PNS demyelination without overt axonal loss. By profiling sensory ganglia at single-cell resolution, we show that glial cell loss induces a transcriptional injury response preferentially in proprioceptive and Aβ RA-LTMR neurons. The transcriptional response of sensory neurons to mechanical injury has been assumed to be a cell-autonomous response. By identifying a similar response in non-injured, demyelinated neurons, our study suggests that this represents a non-cell-autonomous transcriptional response of sensory neurons to glial cell loss and demyelination. [Display omitted] •Peripheral glial cell ablation results in transient demyelination•PNS demyelination initiates a transcriptional injury response in sensory neurons•The injury response occurs predominantly in proprioceptive and Aβ RA-LTMR neurons•Traumatic injury and glial cell loss induce similar neuronal transcriptional responses Using a genetic mouse model of glial cell ablation and demyelination, Elbaz et al. found that demyelinated sensory neurons initiate an injury-induced transcriptional program suggestive of active participation in the remyelination process. Among the sensory neurons, this transcriptional response occurred predominantly in large myelinated proprioceptive and Aβ RA-LTMR neurons.