title: Molecular signatures of mouse TRPV1-lineage neurons revealed by RNA-Seq transcriptome analysis.
abstract: Disorders of pain neural systems are frequently chronic and, when recalcitrant to treatment, can severely degrade the quality of life. The pain pathway begins with sensory neurons in dorsal root or trigeminal ganglia, and the neuronal subpopulations that express the transient receptor potential cation channel, subfamily V, member 1 (TRPV1) ion channel transduce sensations of painful heat and inflammation and play a fundamental role in clinical pain arising from cancer and arthritis. In the present study, we elucidate the complete transcriptomes of neurons from the TRPV1 lineage and a non-TRPV1 neuroglial population in sensory ganglia through the combined application of next-gen deep RNA-Seq, genetic neuronal labeling with fluorescence-activated cell sorting, or neuron-selective chemoablation. RNA-Seq accurately quantitates gene expression, a difficult parameter to determine with most other methods, especially for very low and very high expressed genes. Differentially expressed genes are present at every level of cellular function from the nucleus to the plasma membrane. We identified many ligand receptor pairs in the TRPV1 population, suggesting that autonomous presynaptic regulation may be a major regulatory mechanism in nociceptive neurons. The data define, in a quantitative, cell population-specific fashion, the molecular signature of a distinct and clinically important group of pain-sensing neurons and provide an overall framework for understanding the transcriptome of TRPV1 nociceptive neurons.
  
  
  CONCLUSIONS
  Next-gen RNA-Seq, combined with molecular genetics, provides a comprehensive and quantitative measurement of transcripts in TRPV1 lineage neurons and a contrasting transcriptome from non-TRPV1 neurons and cells. The transcriptome highlights previously unrecognized protein families, identifies multiple molecular circuits for excitatory or inhibitory autocrine and paracrine signaling, and suggests new combinatorial approaches to pain control.
authors.affiliation: Anesthesia Section, Department of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Samridhi C
authors.initials: SC
authors.lastname: Goswami
authors.affiliation: Molecular Genetics Unit, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, Bethesda, Maryland.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Mishra
authors.affiliation: Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
authors.forename: Dragan
authors.initials: D
authors.lastname: Maric
authors.affiliation: Anesthesia Section, Department of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Krisztian
authors.initials: K
authors.lastname: Kaszas
authors.affiliation: Anesthesia Section, Department of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Gonnella
authors.affiliation: Anesthesia Section, Department of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Clokie
authors.affiliation: Anesthesia Section, Department of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Hal D
authors.initials: HD
authors.lastname: Kominsky
authors.affiliation: Anesthesia Section, Department of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jacklyn R
authors.initials: JR
authors.lastname: Gross
authors.affiliation: Anesthesia Section, Department of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Keller
authors.affiliation: Anesthesia Section, Department of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mannes
authors.affiliation: Molecular Genetics Unit, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, Bethesda, Maryland.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hoon
authors.affiliation: Anesthesia Section, Department of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland. Electronic address: michael.iadarola@nih.gov.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Iadarola
mesh_terms: D000818:Animals; D019070:Cell Lineage; D005727:Ganglia, Spinal / Q000378:metabolism*; D015870:Gene Expression; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism*; D010146:Pain / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome; D014276:Trigeminal Nerve / Q000378:metabolism
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C493922:Trpv1 protein, rat
keywords: Pain; capsaicin; dorsal root ganglion; nociception; resiniferatoxin