Stereotyped transcriptomic transformation of somatosensory neurons in response to injury

In mice, spared nerve injury replicates symptoms of human neuropathic pain and induces upregulation of many genes in somatosensory neurons. Here we used single cell transcriptomics to probe the effects of partial infraorbital transection of the trigeminal nerve at the cellular level. Uninjured neurons were unaffected by transection of major nerve branches, segregating into many different classes. In marked contrast, axotomy rapidly transformed damaged neurons into just two new and closely-related classes where almost all original identity was lost. Remarkably, sensory neurons also adopted this transcriptomic state following various minor peripheral injuries. By genetically marking injured neurons, we showed that the injuryinduced transformation was reversible, with damaged cells slowly reacquiring normal gene expression profiles. Thus, our data expose transcriptomic plasticity, previously thought of as a driver of chronic pain, as a programed response to many types of injury and a potential mechanism for regulating sensation during wound healing. Nuclei from trigeminal ganglia from wildtype, spared nerve injury mice (2-, 7-, 21-, and 75 days after injury), chronic itch with facial lesions, and minor facial injury mice were isolated. Neuronal nuclei were purified with anti-NeuN antibody and single nucleus RNA-seq were performed with either the Drop-Seq or 10x Genomics method.