Patch-seq of mouse DRG neurons reveals candidate genes for specific mechanosensory functions

Abstract

A variety of mechanosensory neurons are involved in touch, proprioception and pain. Many molecular components of the mechanotransduction machinery subserving these sensory modalities remain to be discovered. Here, we combined recordings of mechanosensitive (MS) currents in mechanosensory neurons with single cell RNA sequencing. In silico combined analysis with a large-scale dataset enables assigning each transcriptome to DRG genetic clusters. Correlation of current signatures with single-cell transcriptomes provides a one-to-one correspondence between mechanoelectric properties and transcriptomically-defined neuronal populations. Moreover, gene expression differential comparison provides a set of candidate genes for mechanotransduction complexes. Piezo2 was expectedly found to be enriched in rapidly adapting MS current-expressing neurons, whereas Tmem120a and Tmem150c, thought to mediate slow-type MS currents, were uniformly expressed in all neuron subtypes, irrespective of their mechano-phenotype. Further knock-down experiments disqualified them as mediating DRG MS currents. This dataset constitutes an open-resource to explore further the cell-type-specific determinants of mechanosensory properties.