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The transcriptome of TRPV1-positive sensory neurons revealed by subgroup-elimination transcriptomics

ABSTRACT: The transcriptome of TRPV1-positive sensory neurons revealed by subgroup-elimination transcriptomics

PROVIDER: PRJEB6878 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR569987_1.fastq.gz	Fastqsanger.gz
	ERR569987_2.fastq.gz	Fastqsanger.gz
	ERR569988_1.fastq.gz	Fastqsanger.gz
	ERR569988_2.fastq.gz	Fastqsanger.gz
	ERR569989_1.fastq.gz	Fastqsanger.gz

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The transcriptome of TRPV1-positive sensory neurons revealed by subgroup-elimination transcriptomics

2015-12-30 | E-MTAB-2789 | biostudies-arrayexpress

The transcriptome of TRPV1-positive sensory neurons revealed by subgroup-elimination transcriptomics

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

The transcriptome of TRPV1-positive sensory neurons revealed by subgroup-elimination transcriptomics

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iPSC-derived human sensory neurons reveal a subset of TRPV1 antagonists as anti-pruritic compounds

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.

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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.

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Project description:The transcriptome of TRPV1-positive sensory neurons revealed by subgroup-elimination transcriptomics

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Sensory lesioning induces microglial synapse elimination via ADAM10 and fractalkine signaling

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