Unbiased Classification of Sensory Neuron Types by Large-Scale Single-Cell RNA Sequencing

Nat Neurosci. 2015 Jan;18(1):145-53. doi: 10.1038/nn.3881. Epub 2014 Nov 24.

Abstract

The primary sensory system requires the integrated function of multiple cell types, although its full complexity remains unclear. We used comprehensive transcriptome analysis of 622 single mouse neurons to classify them in an unbiased manner, independent of any a priori knowledge of sensory subtypes. Our results reveal eleven types: three distinct low-threshold mechanoreceptive neurons, two proprioceptive, and six principal types of thermosensitive, itch sensitive, type C low-threshold mechanosensitive and nociceptive neurons with markedly different molecular and operational properties. Confirming previously anticipated major neuronal types, our results also classify and provide markers for new, functionally distinct subtypes. For example, our results suggest that itching during inflammatory skin diseases such as atopic dermatitis is linked to a distinct itch-generating type. We demonstrate single-cell RNA-seq as an effective strategy for dissecting sensory responsive cells into distinct neuronal types. The resulting catalog illustrates the diversity of sensory types and the cellular complexity underlying somatic sensation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Cell Size
  • Female
  • Gene Expression / physiology
  • Inflammation / physiopathology
  • Inflammation / psychology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pruritus / physiopathology
  • Pruritus / psychology
  • Sensory Receptor Cells / chemistry*
  • Sensory Receptor Cells / classification*
  • Sequence Analysis, RNA / methods*