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

Summary 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 combine recordings of mechanosensitive (MS) currents in mechanosensory neurons with single-cell RNA sequencing. Transcriptional profiles are mapped onto previously identified sensory neuron types to identify cell-type correlates between datasets. Correlation of current signatures with single-cell transcriptomes provides a one-to-one correspondence between mechanoelectric properties and transcriptomically defined neuronal populations. Moreover, a gene-expression differential comparison provides a set of candidate genes for mechanotransduction complexes. Piezo2 is expectedly found to be enriched in rapidly adapting MS current-expressing neurons, whereas Tmem120a and Tmem150c, thought to mediate slow-type MS currents, are uniformly expressed in all mechanosensory neuron subtypes. Further knockdown experiments disqualify them as mediating MS currents in sensory neurons. This dataset constitutes an open resource to explore further the cell-type-specific determinants of mechanosensory properties.
Graphical abstract
Highlights • Patch-seq is performed on mechanically characterized DRG sensory neurons • Transcriptomically defined neuronal classes and current subtypes are correlated • Datasets of specific transcripts of current subtype-expressing neurons are generated • TACAN (Tmem120a) and Tentonin-3 (Tmem150c) do not contribute to DRG mechano-currents
Mechanosensation is the least understood sensory modality at the molecular level. Parpaite et al. combine single-cell RNA sequencing with mechanosensitive current recordings in cultured sensory neurons. One-to-one correspondence between mechanoelectric properties and single-cell transcriptomes provides a valuable resource for the identification of molecular factors involved in mechanosensation.