Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nociceptor-immune interactomes reveal insult-specific immune signatures of pain

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE255686 | GEO | 2024/05/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Nociceptor HDAC4 regulates inflammatory pain

Project description:Transcriptional alterations are characteristic of persistent pain states but the key regulators remain elusive. Using a conditional knockout (cKO) strategy in mice we sought to determine whether loss of the transcriptional co-repressor histone deacetylase four (HDAC4) would have implications for sensory neuron transcription and nociception. HDAC4 was found to be largely dispensable for transcriptional regulation of naïve sensory neurons but was required for transcriptional responses after injury, with Calca and Trpv1 expression consistently downregulated in HDAC4 cKO compared to littermate controls (0.2-0.44 fold). This downregulation corresponded to reduced sensitivity to capsaicin in vitro (76% +/- 4.4% wildtype capsaicin responders vs 56.9% +/- 4.7% cKO responders) and to reduced thermal hypersensitivity in the complete Freund’s adjuvant model of inflammatory pain (1.3-1.4 fold improvement). These data indicate that HDAC4 is a novel inflammatory pain mediator and may be a good therapeutic target, capable of orchestrating the regulation of multiple downstream effectors. Total RNA was extracted from HDAC4 cKO and HDAC4 fl/fl naïve adult lumbar dorsal root ganglia (n=3/group). mRNA expression was compared using Affymetrix Mouse Gene Arrays (Mouse Gene 2.0ST) run on a GeneChip Fluidics Station 450. Chips were scanned on an Affymetrix GeneChip Scanner.

2015-04-23 | E-GEOD-62405 | biostudies-arrayexpress

A role for fibroblast and mural cell subsets in models of neuropathic pain [scRNA-seq]

Project description:Neuropathic pain is a particularly intractable type of chronic pain that can result from physical nerve damage due to surgery or entrapment. Here, we present data which suggest that a particular subclass of fibroblast and mural cells may be implicated in the sensory neuron dysfunction that is characteristic of this pain state. In a mouse model of traumatic painful neuropathy, we used RNA sequencing, cell sorting and nerve tissue clearing to study mesenchymal lineage cells. We show that Pdgfrb+ fibroblasts and mural cells are increased in number for at least two months post-nerve damage and express high levels of known and putative pro-algesic mediators, which are further upregulated in neuropathy. We go on to demonstrate that a human nerve pericyte line releases a selection of these pro-algesic mediators at protein level. Moreover, conditioned media from stimulated human pericytes induces intra-cellular changes in human induced pluripotent stem cell derived sensory neurons; these changes (phosphorylation of the transcription factor STAT3) have been previously linked to sensory neuron activation. In summary, our data indicate that mesenchymal cell abnormalities should be considered when developing novel strategies to tackle neuropathic pain.

2024-12-19 | GSE283177 | GEO

A role for fibroblast and mural cell subsets in models of neuropathic pain [bulkRNA-seq]

2024-12-19 | GSE283281 | GEO

Modelling inflammation-induced peripheral sensitization in a dish – more complex than expected?

Project description:Peripheral sensitization of nociceptors is believed to be a key driver of chronic pain states. Here, we sought to study the effects of a modified version of inflammatory soup on the excitability of human stem-cell derived sensory neurons. For this, we used a pre-existing and a novel stem cell line, modified to stably express the calcium sensor GCamP6f. Upon treatment with inflammatory soup, we observed no changes in neuronal transcription or functional responses upon calcium imaging, and only a very minor increase in resting membrane potential via whole cell patch clamping. Similarly small changes were observed when treating mouse primary sensory neurons with inflammatory soup. A semi-systematic re-examination of past literature further indicated that observed effects of inflammatory mediators on dissociated sensory neuron cultures are generally very small. We conclude that modelling inflammation-induced peripheral sensitization in vitro is non-trivial and will require careful selection of mediators and/or more complex, multi-cellular setups. Especially in the latter, our novel GCamP6f induced-pluripotent stem cell line may be of value.

2024-08-12 | GSE268585 | GEO

Single cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain [Wafergen]

Project description:Distinct types of dorsal root ganglion sensory neurons may have unique contributions to chronic pain. Identification of primate sensory neuron types is critical for understanding the cellular origin and heritability of chronic pain. However, molecular insights into the primate sensory neurons are missing. Here we classify non-human primate dorsal root ganglion sensory neurons based on their transcriptome and map human pain heritability to neuronal types. First, we identified cell correlates between two major datasets for mouse sensory neuron types. Machine learning exposes an overall cross-species conservation of somatosensory neurons between primate and mouse, although with differences at individual gene level, highlighting the importance of primate data for clinical translation. We map genomic loci associated with chronic pain in human onto primate sensory neuron types to identify the cellular origin of chronic pain. Genome-wide associations for chronic pain converge on two different neuronal types distributed between pain disorders that display different genetic susceptibilities, suggesting both unique and shared mechanisms between different pain conditions.

2021-01-27 | GSE165566 | GEO

Single cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain [SmartSeq2]

2021-01-27 | GSE165553 | GEO

Nociceptor HDAC4 regulates inflammatory pain

2015-04-23 | GSE62405 | GEO

Global transcriptome analysis reveals differences between embryonic and adult dorsal root ganglion axonal mRNAs that are implicated in axonal growth and pain

Project description:Local protein synthesis in sensory neuron axons is necessary for axonal regeneration with the efficiency of regeneration decreasing with age. Because the full repertoire of transcripts in embryonic and adult rat sensory axons is unknown we asked how the pool of mRNAs dynamically changes during ageing. We isolated mRNA from pure axons and growth cones devoid of non-neuronal or cell body contamination. Genome-wide microarray analysis reveals that a previously unappreciated number of transcripts are localised in sensory axons and that this repertoire changes during development toward adulthood. Embryonic sensory axons are enriched in transcripts encoding cytoskeletal-related proteins with a role in axonal outgrowth. Surprisingly, adult axons are highly enriched in mRNAs encoding immune molecules with a role in nociception. To validate our experimental approach we show that Tubulin-beta3 mRNA is present only in embryonic axons where it is locally synthesised. In summary, we show that the population of axonal mRNAs dynamically changes during development, which may partly contribute to the intrinsic capacity of axons at different ages to regenerate after injury and to modulate pain. Pure axonal RNA were extracted from the axons of embryonic and adult dorsal root ganglion neurons, each with 5 biological replicates. The axonal transcriptomes were analysed using Affymetrix Rat Genome 230 2.0 Arrays.

2010-11-23 | E-GEOD-22638 | biostudies-arrayexpress

Global analyses of mRNA expression in human sensory neurons reveals eIF5A as a conserved target for inflammatory pain

Project description:Nociceptors are a type of sensory neurons that is integral to most forms of pain. Targeted disruption of nociceptor sensitization affords unique opportunities to prevent pain. An emerging model for nociceptors are sensory neurons derived from human stem cells. Here, we subjected five groups to high-throughput sequencing: human induced pluripotent stem cells (hiPSCs) prior to differentiation, mature hiPSC-derived sensory neurons, mature co-cultures containing hiPSC-derived astrocytes and sensory neurons, mouse DRG tissues, and mouse DRG cultures. Co-culture of nociceptors and astrocytes promotes expression of transcripts enriched in DRG tissues. Comparisons of the hiPSC models to tissue samples reveals that many key genes linked to pain are present. Marker genes indicative of a range of neuronal subtypes present in the DRG were detected in mature hiPSCs. Intriguingly, translation factors were maintained at consistently high expression levels across species and culture systems. As a proof of concept for the utility of this resource, we validated expression of eukaryotic initiation factor 5A (eIF5A) in DRG tissues and hiPSC samples. eIF5A is subject to a unique post-translational hypusine modification required for its activity. Inhibition of hypusine biosynthesis prevented hyperalgesic priming by inflammatory mediators in vivo. One of two hypusine inhibitors diminished hiPSC activity in vitro. Collectively, our results illuminate the transcriptomes of hiPSC sensory neuron models. We provide a proof of concept for this resource through our investigation of eIF5A. Our findings reveal hypusine as a potential target for inflammation associated pain in males.

2022-06-24 | GSE192566 | GEO

Comprehensive analysis of Long non-coding RNA expression in dorsal root ganglion reveals cell type specificity and dysregulation following nerve injury [human iPS]

Project description:Dorsal root ganglion (DRG) neurons provide connectivity between peripheral tissues and spinal cord. Transcriptional plasticity within DRG sensory neurons after peripheral nerve injury contributes to nerve repair but also leads to maladaptive plasticity, including the development of neuropathic pain. This study presents tissue and neuron specific expression profiling of both known and novel Long Non-Coding RNAs (LncRNAs) in rodent DRG following nerve injury. We have identified a large number of novel LncRNAs expressed within rodent DRG, a minority of which were syntenically conserved between mouse and rat and which including both- intergenic and antisense LncRNAs. We have also identified neuron type-specific LncRNAs in mouse DRG, and LncRNAs that are expressed in human IPS cell-derived sensory neurons. We show significant plasticity in LncRNA expression following nerve injury, which in mouse is strain dependant. This resource is publicly available and will aid future studies of DRG neuron identity and the transcriptional landscape in both naïve and injured DRG.

2017-11-21 | GSE107181 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data