Sex differences in nociceptor translatomes contribute to divergent prostaglandin signaling in male and female mice
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ABSTRACT:
PROVIDER: PRJNA655205 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12385366.fastq.gz | Fastqsanger.gz | |||
| SRR12385367.fastq.gz | Fastqsanger.gz | |||
| SRR12385368.fastq.gz | Fastqsanger.gz | |||
| SRR12385369.fastq.gz | Fastqsanger.gz | |||
| SRR12385370.fastq.gz | Fastqsanger.gz |
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Project description:There are clinically relevant sex differences in acute and chronic pain mechanisms, but we are only beginning to understand their mechanistic basis. Transcriptome analyses of rodent whole dorsal root ganglion (DRG) have revealed sex differences, mostly in immune cells. We examined the transcriptome and translatome of the mouse DRG with the goal of identifying sex differences.
2020-08-05 | GSE155676 | GEO
Project description:Persistent changes in nociceptor translatomes govern hyperalgesic priming in mouse models
| PRJNA1144941 | ENA
Project description:Hyperalgesic priming is a model system that has been widely used to understand plasticity in painful stimulus-detecting sensory neurons, called nociceptors. A key feature of this model system is that following priming, stimuli that do not normally cause hyperalgesia now readily provoke this state. We hypothesized that hyperalgesic priming occurs due to reorganization of translation of mRNA in nociceptors. To test this hypothesis we used paclitaxel treatment as the priming stimulus and translating ribosome affinity purification (TRAP) to measure persistent changes in mRNA translation in Nav1.8+ nociceptors. TRAP sequencing revealed 161 genes with persistently altered mRNA translation in the primed state. We identified Gpr88as upregulated, and Metrn as downregulated. We confirmed a functional role for these genes wherein a GPR88 agonist causes pain only in primed mice, and established hyperalgesic priming is reversed by Meteorin. Our work demonstrates that altered nociceptor translatomes are causative in producing hyperalgesic priming.
2024-08-06 | GSE274093 | GEO
Project description:Hyperalgesic priming is a model system that has been widely used to understand plasticity in painful stimulus-detecting sensory neurons, called nociceptors. A key feature of this model system is that following priming, stimuli that do not normally cause hyperalgesia now readily provoke this state. We hypothesized that hyperalgesic priming occurs due to reorganization of translation of mRNA in nociceptors. To test this hypothesis, we used paclitaxel treatment as the priming stimulus and translating ribosome affinity purification (TRAP) to measure persistent changes in mRNA translation in Nav1.8+ nociceptors. TRAP sequencing revealed 161 genes with persistently altered mRNA translation in the primed state. We identified Gpr88 as upregulated and Metrn as downregulated. We confirmed a functional role for these genes, wherein a GPR88 agonist causes pain only in primed mice and established hyperalgesic priming is reversed by Meteorin. Our work demonstrates that altered nociceptor translatomes are causative in producing hyperalgesic priming.
| S-EPMC11326310 | biostudies-literature
Project description:Translatomes of monocytes and macrophages
| PRJNA879755 | ENA
Project description:Inflammatory pain associated with tissue injury and infection largely results from the heightened sensitivity of the peripheral terminals of nociceptor sensory neurons as a consequence of exposure to inflammatory mediators. Targeting immune-derived inflammatory ligands, such as prostaglandin E2, reduces inflammatory pain, but more effective and safer therapies are needed. However, the diversity of immune cell and sensory neuron types, their ligands, and receptors make it challenging to map the immune mechanisms that contribute to inflammatory pain. We, therefore, used single-cell transcriptomics to explore which specific immune cell types affect the development of pain in diverse inflammatory pain models. We found that both the magnitude of macrophage and neutrophil recruitment and the injury-triggered transcriptional program in Cx3cr1 high and MHCII+ dermal macrophages closely mirror the kinetics of inflammatory pain hypersensitivity. We constructed a comprehensive list of potential cell-cell interactions covering receptors, ligands, and metabolites, and generated injury-specific neuroimmune interactomes based on immune cell and sensory neuron single-cell transcriptomic data. This analysis revealed both interactions common to multiple inflammatory pain models and those specific to a particular condition and uncovered immune mediators not previously identified as pain modulators.
2024-05-28 | GSE255686 | GEO
Project description:RNA modifications are essential for the establishment of cellular identity. Although increasing evidence indicates that RNA modifications control the innate immune response, their role in monocyte-to-macrophage differentiation and polarisation is unclear. We profile translatomes of monocytes and macrophages at resting, pro- and anti-inflammatory states.
2024-02-07 | GSE213204 | GEO
Project description:Nociceptor neurons affect cancer immunosurveillance
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Project description:Unbiased 'omics' techniques, such as next generation RNA-sequencing, can provide entirely novel insights into biological systems. However, cellular heterogeneity presents a significant barrier to analysis and interpretation of these datasets. The neurons of the dorsal root ganglia (DRG) are an important model for studies of neuronal injury, regeneration and pain. The majority of investigators utilize a dissociated preparation of whole ganglia when studying cellular and molecular function. We demonstrate that the standard methods for producing these preparations gives a 10%-neuronal mixture of cells, with the remainder of cells constituting satellite glia and other non-neuronal cell types. Using a novel application of magnetic purification, we consistently obtain over 95% pure, viable neurons from adult tissue, significantly enriched for small diameter nociceptors expressing the voltage gated ion channel Nav1.8. Using genome-wide RNA-sequencing we compare the currently used (10% neuronal) and pure (95% nociceptor) preparations and find 920 genes enriched. This gives an unprecedented insight into the molecular composition of small nociceptive neurons in the DRG, potentially altering the interpretation of previous studies performed at the tissue level, and indicating a number of novel markers of this widely-studied population of cells. We anticipate that the ease of use, affordability and speed of this technique will see it become widely adopted, delivering a greatly improved capacity to study the roles of nociceptors in health and disease. RNA-Seq was performed for 4 biological replicates from three different groups: intact DRG, acutely dissociated DRG and magnetically-purified DRG neurons. Differential expression was analyzed between acutely dissociated and MACS-dissociated samples to define the 'nociceptor transcriptome'.
2014-11-17 | E-GEOD-62424 | biostudies-arrayexpress
Project description:The goal of this study was to analyze global gene expression in specific populations of nociceptor sensory neurons, the neurons that detect damaging/noxious stimuli. The dorsal root ganglia (DRG), trigeminal ganglia, and nodose ganglia are anatomically distinct peripheral sensory ganglia that contain nociceptors which innervate skin, gut, lungs, and other distinct organ tissues. We used flow cytometry to purify nociceptors from these ganglia and profiled their global gene expression signatures to compare gene expression between these different anatomically distinct nociceptors. Nav1.8-Cre were bred with Rosa26-TdTomato to generate Nav1.8-Cre/R26-TdTomato reporter progeny, where all peripheral nociceptor neurons are genetically marked with red fluroescence due to specific expression of the TTX- resistant sodium channel Nav1.8. Lumbar region dorsal root ganglia (DRG), trigeminal ganglia, and nodose ganglia were dissected from mice (3 mice were pooled/sample). Highly red fluorescent neurons were Facs purified, RNA extracted, and processed for microarray analysis.
2013-08-28 | E-GEOD-46546 | biostudies-arrayexpress