Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity
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AutorChiu, Isaac M.; Barrett, Lee B.; Williams, Erika K.; Strochlic, David E.; Lee, Seungkyu; Weyer, Andy D.; Lou, Shan; Bryman, Gregory S.; Roberson, David P.; Ghasemlou, Nader; Piccoli, Cara; Ahat, Ezgi; Wang, Victor; Cobos del Moral, Enrique José; Stucky, Cheryl L.; Ma, Qiufu; Liberles, Stephen D.; Woolf, Clifford J.
Subtype specific genesDorsal root gangliaNociceptive neuronsNeuropathic painSensory neurons
Chiu, I.M.; et al. Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity. Elife, 3: 04660 (2014). [http://hdl.handle.net/10481/34825]
PatrocinadorThis work was supported by CJW NIH R37 NS039518; R01 NS038253; 1PO1 NS072040-01; and the Dr. Miriam and Sheldon G. Adelson Medical Foundation. IMC received fellowship support from NIH F32 NS076297-01. Gene expression analysis were performed in the IDDRC Molecular Genetics Core facility at Boston Children's Hospital, supported by National Institutes of Health award NIH-P50-NS40828. Flow cytometry was performed in the IDDRC Stem Cell Core Facility at Boston Children's Hospital, supported by NIH-P30-HD18655. Microarray work was conducted at the Boston Children's Hospital IDDRC Molecular Genetics Core, supported by NIH-P30-HD 18655.
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.