Single-soma RNA-seq of Human DRG and TG Neurons

Abstract

Primary somatosensory neurons, including dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons, detect internal and external stimuli from the trunk and head of the body, respectively. Currently, the translational success of novel therapeutics developed in pain studies using model organisms has been low, which may be due to species differences in primary somatosensory neurons. Thus, a big question is what the molecular and cellular features of human DRG and TG neurons are. To attempt to reveal the molecular profiles of human primary somatosensory neurons and their functional characteristics, our team used laser capture microdissection (LCM) —which avoided dissociation-related technical issues — to isolate and enrich individual human DRG and TG neuron soma and combined it with Smart-seq2 for deep single-soma RNA sequencing. In addition, we used 10x Xenium spatial transcriptomics to validate the top molecular markers and cell types. Last, we obtained in vivo physiological recordings from human subjects to test the temperature-sensing functional properties of somatosensory afferents from multiple DRG cell types. Our comprehensive approach has led to several key novel findings about human DRG/TG neurons.  <br>