Single cell RNA-seq analysis of sensory neurons reveal diverse injury responses after sciatic nerve transection
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE71453 | GEO | 2016/08/26
SECONDARY ACCESSION(S): PRJNA291276
REPOSITORIES: GEO
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Project description:There are currently no approved treatments for the weakness and paralysis that result from loss of peripheral nerve function with aging, trauma, or neuromuscular disease. Here we use single nuclei sequencing to show that denervation due to transection of the sciatic nerve triggers a striking increase in the prostaglandin degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in skeletal muscle.
2023-10-23 | GSE239848 | GEO
Project description:The goal of this study was to analyze global gene expression in FACS purified Nav1.8 lineage sensory neurons, which include nociceptor neurons that detect damaging/noxious stimuli, following peripheral inflammation by intraplantar injection of Complete Freund's Adjuvant (CFA) or Sciatic Nerve Injury (SNI) by nerve transection. Nav1.8 Trangsgenic TdTomato+ neurons were purified from Lumbar L4-L6 dorsal root ganglia (DRG) by flow cytometry from mice on the ipsilateral or contralateral sides, following Complete Freund's Adjuvant injection (day 1) or sciatic nerve transection (day 5). Neurons were then analyzed for transcriptional gene expression by microarray analysis.
2023-01-30 | GSE221834 | GEO
Project description:Changes in microRNA (miRNA) expression in the mouse L4 and L5 dorsal root ganglion following unilateral sciatic nerve transection. The timepoint of 7 days post-axotomy was chosen to capture miRNA expression profiles at a time when the injured neurons were beginning to regenerate. Two condition experiment, paired control DRG vs axotomised DRG following unilateral sciatic nerve transection. 3 biological replicates, one replicate per array. Dye swap in Replicate 2.
2011-05-06 | E-GEOD-29096 | biostudies-arrayexpress
Project description:Peripheral nerve repair and functional recovery depend on the rate of nerve regeneration and the quality of target reinnervation. It is important to fully understand the cellular and molecular basis underlying the specificity of peripheral nerve regeneration, which means the achieving of respective correct pathfinding and accurate target reinnervation for regrowing motor and sensory axons. In this study, a quantitative proteomic technique, based on isobaric tags for relative and absolute quantitation (iTRAQ) was used to profile the protein expression pattern between single motor and sensory nerves at 14 days after peripheral nerve transection. Among a total of 1259 proteins identified, 176 proteins showed the differential expressions between injured motor and sensory nerves. Quantitative real-time RT-PCR and Western blot analysis were applied to validate the proteomic data on representative differentially expressed proteins. Functional categorization indicated that differentially expressed proteins were linked to a diverse array of molecular functions, including axonogenesis, response to axon injury, tissue remodeling, axon ensheathment, cell proliferation and adhesion, vesicle-mediated transport, response to oxidative stress, internal signal cascade, and macromolecular complex assembly, which might play an essential role in peripheral motor and sensory nerve regeneration. Overall, we hope that the proteomic database obtained in this study could serve as a solid foundation for the comprehensive investigation of differentially expressed proteins between injured motor and sensory nerves and for the mechanism elucidation of the specificity of peripheral nerve regeneration.
2020-12-10 | PXD022097 | Pride
Project description:Changes in microRNA (miRNA) expression in the mouse L4 and L5 dorsal root ganglion following unilateral sciatic nerve transection. The timepoint of 7 days post-axotomy was chosen to capture miRNA expression profiles at a time when the injured neurons were beginning to regenerate.
2011-05-06 | GSE29096 | GEO
Project description:Analysis of extruded axoplasm proteomes from adult rat sciatic nerves in vivo by Label Free Quantitative Proteomics (LFQ) and comparison of normal and injury (18 hours post complete nerve transection) conditions. A combination of BONCAT and MS/MS were also performed to analyze the top axonal newly synthetized proteins in vivo.
2020-11-18 | MSV000086475 | MassIVE
Project description:Axon degeneration underlies many nervous system diseases; therefore understanding the regulatory signalling pathways is fundamental to identifying potential therapeutics. Previously, we demonstrated heparan sulphates (HS) as a potentially new target for promoting CNS repair. HS modulate cell signalling by both acting as cofactors in the formation of ligand-receptor complexes and in sequestering ligands in the extracellular matrix. The enzyme heparanase (Hpse) negatively regulates these processes by cleaving HS and releasing the attached proteins, thereby attenuating their ligand-receptor interaction. To explore a comparative role for HS in PNS axon injury/repair we data mined published microarrays from distal sciatic nerve injury. We identified Hpse as a previously unexplored candidate, being up-regulated following injury. We confirmed these results and demonstrated inhibition of Hpse led to an acceleration of axonal degeneration, accompanied by an increase in ?-catenin. Inhibition of ?-catenin and the addition of Heparinase I both attenuated axonal degeneration. Furthermore the inhibition of Hpse positively regulates transcription of genes associated with peripheral neuropathies and Schwann cell de-differentiation. Thus, we propose Hpse participates in the regulation of the Schwann cell injury response and axo-glia support, in part via the regulation of Schwann cell de-differentiation and is a potential therapeutic that warrants further investigation.
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Project description:BackgroundPeripheral nerves can self-regenerate after traumatic injury, although their self-regeneration ability is limited after severe nerve injury. After peripheral nerve injury, the distal nerve stumps undergo Wallerian degeneration while the proximal nerve stumps undergo a regeneration process.MethodsHere, to decipher genetic changes and involved biological processes in the proximal nerve stumps after peripheral nerve injury, microarray data (GSE30165) were analyzed. Differentially expressed genes in the proximal nerve stumps at 0.5 h, 1 h, 3 h, 6 h, 9 h, 1 d, 4 d, 7 d, and 14 d after rat sciatic nerve transection were subjected to Ingenuity pathway analysis (IPA) bioinformatic analysis.ResultsCytokine signaling, cellular immune response, nuclear receptor signaling, disease-specific pathways, and organismal growth and development were significantly activated in the proximal nerve stumps after nerve transection. Organ development, inflammation and immune response, diseases and organ abnormalities, and cellular behavior-related biological functions were highly involved.ConclusionsThe expression levels of differentially expressed genes in biological function "Organismal Injury and Abnormalities" were displayed and validated. Our current study helps to obtain a better understanding of the biological processes of peripheral nerve regeneration, especially the regeneration process in the proximal nerve stumps, and thus may help to discover new therapeutic methods that can promote nerve regeneration.
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Project description:A major risk factor for glaucomatous optic neuropathy is the level of intraocular pressure (IOP), which can lead to retinal ganglion cell axon injury and cell death. The optic nerve has a rostral unmyelinated portion at the optic nerve head followed by a caudal myelinated region. The unmyelinated region is differentially susceptible to IOP-induced damage in rodent models and in human glaucoma. While several studies have analyzed gene expression changes in the mouse optic nerve following optic nerve injury, few were designed to consider the regional gene expression differences that exist between these distinct areas. We performed bulk RNA-sequencing on the retina and on separately micro-dissected unmyelinated and myelinated optic nerve regions from naïve C57BL/6 mice, mice after optic nerve crush, and mice with microbead-induced experimental glaucoma (total = 36). Gene expression patterns in the naïve unmyelinated optic nerve showed significant enrichment of the Wnt, Hippo, PI3K-Akt, and transforming growth factor β pathways, as well as extracellular matrix–receptor and cell membrane signaling pathways, compared to the myelinated optic nerve and retina. Gene expression changes induced by both injuries were more extensive in the myelinated optic nerve than the unmyelinated region, and greater after nerve crush than glaucoma. Changes present three and fourteen days after injury largely subsided by six weeks. Gene markers of reactive astrocytes did not consistently differ between injury states. Overall, the transcriptomic phenotype of the mouse unmyelinated optic nerve was significantly different from immediately adjacent tissues, likely dominated by expression in astrocytes, whose junctional complexes are inherently important in responding to IOP elevation.
2023-09-06 | GSE241782 | GEO
Project description:Peripheral nervous system owns the ability of self-regeneration, mainly in its regenerative microenvironment including vascular network reconstruction. More recently, more attentions have been given to the close relationship between tissue regeneration and angiogenesis. To explore the overlap of molecular mechanisms and key regulation molecules between peripheral nerve regeneration and angiogenesis post peripheral nerve injury, integrative and bioinformatic analysis was carried out for microarray data of proximal stumps after sciatic nerve transection in SD rats. Nerve regeneration and angiogenesis were activated at 1 day immediately after sciatic nerve transection simultaneously. The more obvious changes of transcription regulators and canonical pathways suggested a phase transition between 1 and 4 days of both nerve regeneration and angiogenesis after sciatic nerve transection. Furthermore, 16 differentially expressed genes participated in significant biological processes of both nerve regeneration and angiogenesis, a few of which were validated by qPCR and immunofluorescent staining. It was demonstrated that STAT3, EPHB3, and Cdc42 co-expressed in Schwann cells and vascular endothelial cells to play a key role in regulation of nerve regeneration and angiogenesis simultaneously response to sciatic nerve transection. We provide a framework for understanding biological processes and precise molecular correlations between peripheral nerve regeneration and angiogenesis after peripheral nerve transection. Our work serves as an experimental basis and a valuable resource to further understand molecular mechanisms that define nerve injury-induced micro-environmental variation for achieving desired peripheral nerve regeneration.
| S-EPMC5649188 | biostudies-literature