The transcriptome of TRPV1-positive sensory neurons revealed by subgroup-elimination transcriptomics
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE59727 | GEO | 2015/05/12
SECONDARY ACCESSION(S): PRJNA256086
REPOSITORIES: GEO
Similar Datasets
Project description:We developed an approach to rapidly eliminate the subgroup of sensory neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia using agonist treatment followed by density centrifugation. To identify transcripts predominantly expressed in TRPV1-positive neurons, we compared the transcriptome of all cells within sensory ganglia versus all cells without TRPV1 expressing neurons using RNA-Seq.
2015-12-30 | E-MTAB-2789 | biostudies-arrayexpress
Project description:We developed an approach to rapidly eliminate the subgroup of sensory neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia using agonist treatment followed by density centrifugation. To identify transcripts predomintly expressed in TRPV1-positive neurons, we compared the transcriptome of all cells within sensory ganglia versus all cells without TRPV1 expressing neurons using RNA-Seq. Four replicate experiments with RNA from DRG neurons of one rat per experiment were performed. Dissociated neurons were split up in three parts, treated with solvent DMSO (0.1%), casaicin (10 µM), or RTX (100 nM) for 30 min followed by gradient centrifugation. RNA was extracted from the remaining pellet containing either all cells or all cells without TRPV1-positive neurons.
2015-05-12 | E-GEOD-59727 | biostudies-arrayexpress
Project description:Capsaicin-sensitive (Trpv1-positive) sensory C-fibers derived from vagal ganglia innervate the visceral organs, and respond to inflammatory mediators and noxious stimuli. These neurons play an important role in maintenance of visceral homeostasis, and contribute to the symptoms of visceral inflammatory diseases. Vagal sensory neurons are located in two ganglia, the jugular ganglia (derived from the neural crest), and the nodose ganglia (from the epibranchial placodes). The functional difference, especially in response to immune mediators, between jugular and nodose neurons is not fully understood. In this study, we microscopically isolated murine nodose and jugular capsaicin-sensitive / Trpv1-expressing C-fiber neurons and performed transcriptome profiling using ultra-low input RNA sequencing.
2017-10-01 | GSE102123 | GEO
Project description:Visceral sensory neurons encode distinct sensations from healthy organs and initiate pain states that are resistant to common analgesics. Transcriptome analysis is transforming our understanding of sensory neuron subtypes but has generally focused on somatic sensory neurons or the total population of neurons in which visceral neurons form the minority. Our aim was to define transcripts specifically expressed by sacral visceral sensory neurons, as a step towards understanding the unique biology of these neurons and potentially lead to identification of new analgesic targets for pelvic visceral pain. Our strategy was to identify genes differentially expressed between sacral dorsal root ganglia (DRG) that include somatic neurons and sacral visceral neurons, and adjacent lumbar DRG that comprise exclusively somatic sensory neurons. This was performed in male and female mice (adult and E18.5). By developing a method to restrict analyses to nociceptive Trpv1 neurons, a larger group of genes were detected as differentially expressed between spinal level. We identified many novel genes not previously been associated with pelvic visceral sensation or nociception. Limited sex differences were detected across the transcriptome of sensory ganglia, but more were revealed in sacral levels and especially in Trpv1 nociceptive neurons. These data will facilitate development of new tools to modify mature and developing sensory neurons and nociceptive pathways.
2020-03-02 | GSE131621 | GEO
Project description:The transcriptome of TRPV1-positive sensory neurons revealed by subgroup-elimination transcriptomics
| PRJEB6878 | ENA
Project description:Given the inaccessibility of human sensory neurons (SNs), it is yet to be established whether the signalling pathway between histamine 1 receptor (H1R) and transient receptor potential cation channel subfamily V member 1 (TRPV1) is conserved between humans and mammalian models. Accessible human SNs are vital for identifying TRPV1 antagonists with higher potential for success in clinical trials targeting histaminergic itch, especially given TRPV1's species specificity concerns. Hence to build a humanized histamine-dependent itch model, we derived peripheral sensory neurons from human pluripotent stem cells (hiPSC-SNs) and validated channel functionality using immunostaining, calcium imaging and multielectrode array (MEA) recordings. Here, we demonstrated that a subset of hiPSC-SNs exhibits co-expression of H1R and TRPV1, responding to both histamine and capsaicin agonists. We found that inhibiting TRPV1 prevented histamine activation. Moreover, we show that silencing histamine-sensitive neurons reduces capsaicin response, and silencing capsaicin-sensitive neurons diminishes histamine response. To assess the ability of hiPSC-SNs in TRPV1 antagonist drug screening, we evaluated two well-established hyperthermic and three thermal-neutral TRPV1 antagonists. Our finding identifies SB366791, a thermal-neutral antagonist, as a potent inhibitor of H1R activation. The use of hiPSC-SNs may therefore provide a physiologically relevant means to perform large-scale screening to discover anti-pruritic agents predictive of actual efficacy in human clinical trials.
2024-02-27 | GSE256435 | GEO
Project description:Vampire bats and snakes have taken thermosensation to the extreme by developing specialized systems for detecting infrared radiation. As such, these creatures provide a window into the molecular and genetic mechanisms underlying evolutionary tuning of thermoreceptors in a species or cell type specific manner. In each case, robust thermal sensitivity likely reflects specialized anatomical features of infrared sensing pit organs, as well as intrinsic heat sensitivity of trigeminal nerve fibers that innervate these structures. Here we show that vampire bats use a molecular strategy involving alternative splicing of the TRPV1 gene to generate a channel specifically within trigeminal ganglia that has a reduced thermal activation threshold. Selective expression of splicing factors in trigeminal, but not dorsal root ganglia, together with unique organization of the vampire bat TRPV1 gene underlies this mechanism of sensory adaptation. Comparative genomic analysis of the TRPV1 locus supports phylogenetic relationships within the proposed Pegasoferae clade of mammals. Gene expression measurements implicate a TRPV1 splice isoform as the heat-sensitive channel in vampire bats
2011-08-04 | E-GEOD-28243 | biostudies-arrayexpress
Project description:Vagal afferent neurons are thought to convey primarily physiological information, whereas spinal afferents transmit noxious signals from the viscera to the central nervous system. In order to elucidate molecular identities for these different properties, we compared gene expression profiles of neurons located in nodose ganglia (NG) and dorsal root ganglia (DRG) in mice. Intraperitoneal administration of Alexa Fluor-488 conjugated Cholera toxin B allowed identification of neurons projecting to the viscera. Fluorescent neurons in DRG (from T10 to T13) and NG were isolated using laser capture microdissection. Gene expression profiles of visceral afferent neurons, obtained by microarray hybridization, were analysed using multivariate spectral map analysis, SAM algorithm (Significance Analysis of Microarray data) and fold-difference filtering. A total of 1996 genes were found to be differentially expressed in DRG versus NG, including 41 G-protein coupled receptors and 60 ion channels. Expression profiles obtained on laser-captured neurons were contrasted to those obtained on whole ganglia demonstrating striking differences and the need for microdissection when studying visceral sensory neurons because of dilution of the signal by somatic sensory neurons. Furthermore, a detailed catalogue of all adrenergic and cholinergic, GABA, glutamate, serotonin and dopamine receptors, voltage-gated potassium, sodium and calcium channels and transient receptor potential cation channels present in visceral afferents is provided. Our genome-wide expression profiling data provide novel insight into molecular signatures that underlie both functional differences and similarities between NG and DRG visceral sensory neurons. Moreover, these findings will offer novel insight into mode of action of pharmacologic agents modulating visceral sensation. Experiment Overall Design: Three separate experiments were performed. First, 5 whole dorsal root ganglia were compared to 7 whole nodose ganglia. Second, Laser captured visceral neurons derived from 5 dorsal root ganglia and 5 nodose ganglia were compared on MG-U74Av2. Third, Laser captured visceral neurons derived from 9 dorsal root ganglia and 11 nodose ganglia were compared on Mouse430_2.
2007-08-31 | E-GEOD-2917 | biostudies-arrayexpress
Project description:Vampire bats and snakes have taken thermosensation to the extreme by developing specialized systems for detecting infrared radiation. As such, these creatures provide a window into the molecular and genetic mechanisms underlying evolutionary tuning of thermoreceptors in a species or cell type specific manner. In each case, robust thermal sensitivity likely reflects specialized anatomical features of infrared sensing pit organs, as well as intrinsic heat sensitivity of trigeminal nerve fibers that innervate these structures. Here we show that vampire bats use a molecular strategy involving alternative splicing of the TRPV1 gene to generate a channel specifically within trigeminal ganglia that has a reduced thermal activation threshold. Selective expression of splicing factors in trigeminal, but not dorsal root ganglia, together with unique organization of the vampire bat TRPV1 gene underlies this mechanism of sensory adaptation. Comparative genomic analysis of the TRPV1 locus supports phylogenetic relationships within the proposed Pegasoferae clade of mammals.
2011-08-04 | GSE28243 | GEO
Project description:Visceral sensory neurons encode distinct sensations from healthy organs and initiate pain states that are resistant to common analgesics. Transcriptome analysis is transforming our understanding of sensory neuron subtypes but has generally focused on somatic sensory neurons or the total population of neurons in which visceral neurons form the minority. Our aim was to define transcripts specifically expressed by sacral visceral sensory neurons, as a step towards understanding the unique biology of these neurons and potentially lead to identification of new analgesic targets for pelvic visceral pain. Our strategy was to identify genes differentially expressed between sacral dorsal root ganglia (DRG) that include somatic neurons and sacral visceral neurons, and adjacent lumbar DRG that comprise exclusively somatic sensory neurons. This was performed in male and female mice (adult and E18.5). By developing a method to restrict analyses to nociceptive Trpv1 neurons, a larger group of genes were detected as differentially expressed between spinal level. We identified many novel genes not previously been associated with pelvic visceral sensation or nociception. Limited sex differences were detected across the transcriptome of sensory ganglia, but more were revealed in sacral levels and especially in Trpv1 nociceptive neurons. These data will facilitate development of new tools to modify mature and developing sensory neurons and nociceptive pathways.
2020-03-02 | GSE131622 | GEO