Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity

Elife. 2014 Dec 19:3:e04660. doi: 10.7554/eLife.04660.

Abstract

The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4(+)SNS-Cre/TdTomato(+), 2) IB4(-)SNS-Cre/TdTomato(+), and 3) Parv-Cre/TdTomato(+) cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation.

Keywords: DRG; evolutionary biology; genomics; mouse; neuroscience; nociception; peripheral nervous system; proprioception; somatosensation; transcriptome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Separation
  • Cluster Analysis
  • Flow Cytometry
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / metabolism
  • Gene Expression Profiling*
  • Mice
  • Patch-Clamp Techniques
  • Principal Component Analysis
  • Sensory Receptor Cells / metabolism*
  • Transcription, Genetic*