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

被引:1482
作者
Usoskin, Dmitry [1 ]
Furlan, Alessandro [1 ]
Islam, Saiful [1 ]
Abdo, Hind [1 ]
Lonnerberg, Peter [1 ]
Lou, Daohua [1 ]
Hjerling-Leffler, Jens [1 ]
Haeggstrom, Jesper [2 ]
Kharchenko, Olga [1 ]
Kharchenko, Peter V. [3 ,4 ]
Linnarsson, Sten [1 ]
Ernfors, Patrik [1 ]
机构
[1] Karolinska Inst, Dept Med Biochem & Biophys, Div Mol Neurobiol, Stockholm, Sweden
[2] Karolinska Inst, Dept Med Biochem & Biophys, Div Physiol Chem, Stockholm, Sweden
[3] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA
[4] Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA
基金
瑞典研究理事会; 欧洲研究理事会;
关键词
GASTRIN-RELEASING-PEPTIDE; LYSOPHOSPHATIDIC ACID; NOCICEPTIVE NEURONS; SOMATIC SENSATIONS; NEUROPATHIC PAIN; ITCH SENSATION; NOXIOUS HEAT; SPINAL-CORD; RECEPTOR; SEQ;
D O I
10.1038/nn.3881
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:145 / +
页数:11
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