Cited by 2,136Single-cell and spatial transcriptomicsIon Channels and ReceptorsPain Mechanisms and Treatments

Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing

Usoskin, Dmitry, Furlan, Alessandro, Islam, Saiful, Abdo, Hind, Lönnerberg, Peter, Lou, Daohua, Hjerling-Leffler, Jens, Haeggström, Jesper +4 more·2015·Nature Neuroscience

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.

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Crossref · 10.1038/nn.3881

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2 of 2 references verified0 citation errors · 0 not checkable

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  • The division of peripheral sensory neurons suggests refinements to previous classifications.

    “Within the peripheral sensory neurons (of the dorsal root ganglia), cell types were divided into three main branches: peptidergic (eight types), non-peptidergic (six types), and neurofilament (three types), which suggests refinements to previous classifications (Li et al., 2016, Usoskin et al., 2015) (Figure S4 and Table S2).”

    From Molecular Architecture of the Mouse Nervous System (2018) · cites this paper as Usoskin et al., 2015

  • Within the peripheral sensory neurons (of the dorsal root ganglia), cell types were divided into three main branches: peptidergic (eight types), non-peptidergic (six types), and neurofilament (three types).

    “Within the peripheral sensory neurons (of the dorsal root ganglia), cell types were divided into three main branches: peptidergic (eight types), non-peptidergic (six types), and neurofilament (three types), which suggests refinements to previous classifications (Li et al., 2016, Usoskin et al., 2015) (Figure S4 and Table S2).”

    From Molecular Architecture of the Mouse Nervous System (2018) · cites this paper as Usoskin et al., 2015

  • t-SNE is a powerful nonlinear dimensionality-reduction alternative, especially when computed with an efficient approximation that scales to large genomic data sets.

    “A powerful, nonlinear alternative5,105–107 is t-distributed stochastic neighbor embedding108 (t-SNE; introduced for single-cell analysis as viSNE105), especially when computed with an efficient approximation109 compatible with the scale of large genomic data sets110.”

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Authors
Usoskin, D., Furlan, A., Islam, S., Abdo, H., Lönnerberg, P., Lou, D., Hjerling-Leffler, J., Haeggström, J., Kharchenko, O., Kharchenko, P. V., Linnarsson, S., & Ernfors, P.
Affiliations
  • Karolinska Institutet (SE)
  • Boston Children's Hospital (US)
Corresponding author
  • Linnarsson, Sten
  • Ernfors, Patrik
Venue
Nature Neuroscience
Published
2014-11-24
Volume
18
Issue
1
Pages
145-153
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2033072655
Cited by
2,136
References
2
Citations by year
2026: 181 · 2025: 168 · 2024: 183 · 2023: 212 · 2022: 206 · 2021: 250 · 2020: 247 · 2019: 186 · 2018: 182 · 2017: 145 · 2016: 106 · 2015: 63 · 2014: 3
FWCI
43.08
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Stiftelsen för Strategisk Forskning
  • Vetenskapsrådet
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords
sensory neurons, primary afferent neurons, mechanoreceptors, nociceptors, thermosensitive neurons, proprioception, transcriptome, atopic dermatitis, mice
MeSH terms
Animals, Behavior, Animal, Female, Inflammation, Male, Mice, Inbred C57BL, Pruritus, Sensory Receptor Cells, Gene Expression, Sequence Analysis, RNA, Cell Size, Mice

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