National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA.
National Center for Complementary and Integrative Health, Bethesda, MD 20892, USA.
Neuron. 2021 Jan 20;109(2):285-298.e5. doi: 10.1016/j.neuron.2020.10.028. Epub 2020 Nov 12.
Single-cell RNA-sequencing and in vivo functional imaging provide expansive but disconnected views of neuronal diversity. Here, we developed a strategy for linking these modes of classification to explore molecular and cellular mechanisms responsible for detecting and encoding touch. By broadly mapping function to neuronal class, we uncovered a clear transcriptomic logic responsible for the sensitivity and selectivity of mammalian mechanosensory neurons. Notably, cell types with divergent gene-expression profiles often shared very similar properties, but we also discovered transcriptomically related neurons with specialized and divergent functions. Applying our approach to knockout mice revealed that Piezo2 differentially tunes all types of mechanosensory neurons with marked cell-class dependence. Together, our data demonstrate how mechanical stimuli recruit characteristic ensembles of transcriptomically defined neurons, providing rules to help explain the discriminatory power of touch. We anticipate a similar approach could expose fundamental principles governing representation of information throughout the nervous system.
单细胞 RNA 测序和体内功能成像为神经元多样性提供了广泛但不相关的视角。在这里，我们开发了一种将这些分类模式联系起来的策略，以探索负责检测和编码触觉的分子和细胞机制。通过广泛地将功能映射到神经元类型，我们揭示了一个明确的转录组逻辑，负责哺乳动物机械感觉神经元的敏感性和选择性。值得注意的是，具有不同基因表达谱的细胞类型通常具有非常相似的特性，但我们也发现了具有专门和不同功能的转录相关神经元。将我们的方法应用于基因敲除小鼠表明，Piezo2 以显著的细胞类依赖性差异调节所有类型的机械感觉神经元。总之，我们的数据表明，机械刺激如何招募具有特征性转录定义神经元的集合，为帮助解释触觉的辨别力提供了规则。我们预计类似的方法可以揭示整个神经系统中信息表示的基本原理。
