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

Cell Rep. 2021 Nov 2;37(5):109914. doi: 10.1016/j.celrep.2021.109914.

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 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.

Keywords: dorsal root ganglion; ion channel; mechanotransduction; nociception; pain; sensory neuron; somatosensation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / metabolism*
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Male
  • Mechanotransduction, Cellular / genetics*
  • Membrane Potentials
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NIH 3T3 Cells
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • RNA-Seq
  • Single-Cell Analysis
  • Transcriptome*

Substances

  • Ion Channels
  • Membrane Proteins
  • Piezo2 protein, mouse
  • TTN3 protein, mouse
  • Tmem120A protein, mouse