title: Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing.
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.
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Usoskin
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Furlan
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Saiful
authors.initials: S
authors.lastname: Islam
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Hind
authors.initials: H
authors.lastname: Abdo
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Lönnerberg
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Daohua
authors.initials: D
authors.lastname: Lou
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jens
authors.identifier: 0000000245391776
authors.initials: J
authors.lastname: Hjerling-Leffler
authors.affiliation: Division of Physiological Chemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jesper
authors.initials: J
authors.lastname: Haeggström
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Olga
authors.initials: O
authors.lastname: Kharchenko
authors.affiliation: 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA. [2] Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Peter V
authors.initials: PV
authors.lastname: Kharchenko
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sten
authors.initials: S
authors.lastname: Linnarsson
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Ernfors
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D048429:Cell Size; D005260:Female; D015870:Gene Expression / Q000502:physiology; D007249:Inflammation / Q000503:physiopathology / Q000523:psychology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011537:Pruritus / Q000503:physiopathology / Q000523:psychology; D011984:Sensory Receptor Cells / Q000737:chemistry* / Q000145:classification*; D017423:Sequence Analysis, RNA / Q000379:methods*