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

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 the loss of axon-glial cell interactions. Single-nucleus RNA sequencing were performed on dorsal root ganglia from PLP-CreERT;ROSA26-eGFP-DTA mice, a genetic model of Schwann cell and satellite glial cell ablation.