Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity

整个群体和单细胞水平的转录分析揭示了体感神经元的分子多样性

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作者:Isaac M Chiu, Lee B Barrett, Erika K Williams, David E Strochlic, Seungkyu Lee, Andy D Weyer, Shan Lou, Gregory S Bryman, David P Roberson, Nader Ghasemlou, Cara Piccoli, Ezgi Ahat, Victor Wang, Enrique J Cobos, Cheryl L Stucky, Qiufu Ma, Stephen D Liberles, Clifford J Woolf

Abstract

The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4(+)SNS-Cre/TdTomato(+), 2) IB4(-)SNS-Cre/TdTomato(+), and 3) Parv-Cre/TdTomato(+) cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation.

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