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

Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing
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DOI:
10.1038/nn.3881
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发表时间:
2015-01-01
影响因子:
25
通讯作者:
Ernfors, Patrik
Ernfors, Patrik
中科院分区:
医学1区
文献类型:
--
作者:
Usoskin, Dmitry;Furlan, Alessandro;Ernfors, Patrik

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初级感觉系统需要多种细胞类型的集成功能,尽管其全部复杂性仍不清楚。我们对 622 个单个小鼠神经元进行了全面的转录组分析,以公正的方式对它们进行分类,独立于任何感觉亚型的先验知识。我们的结果揭示了 11 种类型:三种不同的低阈值机械感受神经元,两种本体感受神经元,以及六种主要类型的热敏、瘙痒敏感、C 型低阈值机械敏感和伤害感受神经元,它们具有明显不同的分子和操作特性。我们的结果证实了先前预期的主要神经元类型,还对新的、功能不同的亚型进行了分类并提供了标记。例如,我们的结果表明,炎症性皮肤病(例如特应性皮炎)期间的瘙痒与独特的瘙痒产生类型有关。我们证明单细胞 RNA-seq 是一种将感觉反应细胞解剖成不同神经元类型的有效策略。由此产生的目录说明了感觉类型的多样性和躯体感觉背后的细胞复杂性。
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.