Project description:ChIP-seq of H3K4me3 in rat peripheral nerve was used to identify transcription start sites associated with Schwann cell-expressed genes. The analysis was performed in injured and control nerve to identify injury-responsive changes in Schwann cells. H3K4me3 ChIP samples were prepared from rat sciatic nerve at 1 day post-transection using both the distal stump of the injured nerve and the contralateral (sham) nerve.
Project description:Peripheral nerve injuries are common in modern society. The patients may suffer from partial or total loss of sensory, motor and autonomic function in the involved segments of the body. However, The molecular mechanisms of the regeneration program has not yet been definitively clarified and the comprehensive lncRNA expression signature in peripheral nerve regeneration remains fully unknown.We performed a high throughput microarray assay to detect lncRNA expression profile in the distal end of peripheral nerve at 0,3,7,14 day after injury.
Project description:Transcriptional changes are distinct in female and male mice in the time course of peripheral nerve injury response. Here, we present sexually dimorphic transcriptome profiles established in the space of 24 h period after sciatic nerve axotomy.
Project description:Transcriptional changes are distinct in female and male mice in the time course of peripheral nerve injury response. Here, we present sexually dimorphic transcriptome profiles established in the space of 24 h period after sciatic nerve axotomy.
Project description:ChIP-seq of H3K27acetylation in sham and injured nerve. Schwann cells play an important role in the response of peripheral nerve to injury. This study was designed to identify enhancers that are altered in sciatic nerve at 3 days post-injury to help identify pathways that mediate the gene expression reprogramming that occurs in Schwann cells after nerve injury. We employed ChIP-seq analysis of H3K27 acetylation as a mark of actively engaged enhancers, and compared enhancers in the distal stump of transected sciatic nerve compared to contralateral (sham) condition.
Project description:Proteomic analysis of injured human peripheral nerves, particularly focusing on events occurring in the proximal and distal nerve ends, remains relatively underexplored. This study aimed to investigate the molecular patterns underlying a digital nerve injury, concentrating on differences in protein expression between the proximal and distal nerve ends. A total of 26 human injured digital nerve samples (24 men; 2 women; median age 47 [30-66] years), harvested during primary nerve repair within 48 hours post-injury from proximal and distal nerve ends, were analyzed using mass spectrometry. A total of 3914 proteins were identified, with 127 proteins showing significant differences in abundance between the proximal and the distal nerve ends. The downregulation of proteins in the distal nerve end was associated with synaptic transmission, autophagy, neurotransmitter regulation, cell adhesion and migration. Conversely, proteins upregulated in the distal nerve end were implicated in cellular stress response, neuromuscular junction stability and muscle contraction, neuronal excitability and neurotransmitter release, synaptic vesicle recycling and axon guidance and angiogenesis. Investigation of proteins, with functional annotations analysis, in proximal and the distal ends of human injured digital nerves, revealed dynamic cellular responses aimed at promoting tissue degeneration and restoration, while suppressing non-essential processes.
Project description:Wallerian degeneration (WD) involves the fragmentation of axonal segments disconnected from their cell bodies, segmentation of the myelin sheath, and removal of debris by Schwann cells and immune cells. The removal and downregulation of myelin-associated inhibitors of axonal regeneration and synthesis of growth factors by these two cell types are critical responses to successful nerve repair. Here, we analyzed the transcriptome of the sciatic nerve of mice carrying the Wallerian degeneration slow (WldS) mutant gene, a gene that confers axonal protection in the distal stump after injury, therefore causing significant delays in WD, neuroinflammation, and axonal regeneration. 56 C57BL6 mice and 56 C57BL/6 OlaHsd-Wlds mice were anesthetized with isoflurane and underwent a microcrush lesion of their left sciatic nerve at the mid-thigh level (exept naive mice, t0). At 0, 3, 7 and 14 days post-injury, mice were anesthetized and killed by cervical dislocation. Sciatic nerves were collected and conective tissue removed. A 4-mm long sciatic nerve segment was taken from the nerve distal stump, starting at 1 mm distal from the lesion up to 5 mm distal. Distal nerve stumps were pooled by group and RNA extracted. Samples were hybridized to GeneChip® Mouse Genome 430 2.0 Array (Affymetrix). Biological replicate was done.
Project description:Our comprehensive proteomic analysis of mouse sciatic nerves following Spared Nerve Injury (SNI) reveals new dimensions of the molecular mechanisms underlying peripheral nerve injury, shaped by sex, developmental stage, and progression over time. Building on our previous work profiling naïve sciatic nerves (Xian et al., 2022), this study provides a uniquely longitudinal proteomic perspective on sciatic nerve injury, capturing both acute (7 to 14 days post SNI) and chronic (98 days post SNI) proteome changes. By integrating MEFISTO, a time-aware latent factor model, we uncovered intricate proteome dynamics and identified conserved patterns of reorganization. Notably, a robust sex-shared response emerged, reflecting sequential transitions: from early neuronal injury/repair and metabolic adjustments to late-stage structural and transcriptional remodeling alongside sterile inflammation. In addition, observed sex-biased differences in immune and neuronal function further refine our knowledge of divergent aspects of peripheral nerve injury. In summary, we provide an expansive resource, which advances our understanding how demographic variables shape longitudinal peripheral nerve plasticity, associated pathologies, and possibly regeneration. Importantly, our study highlights the opportunities of inclusive, temporally resolved experimental designs in preclinical research.
Project description:To explore the effect of magnetic mechanical force mediated by magnetic nanoparticles in a gradient magnetic field environment on the repair phenotype of Schwann cells in injured sciatic nerves, we established a rat sciatic nerve crush injury model and locally injected magnetic nanoparticles under the epineurium at the distal end of the crush site.
Project description:To map the loci of B2-SINE expressed in DRG which are regulated by sciatic nerve injury, paired-end RNAseq was carried on DRG neurons following sciatic nerve injury at 24h and 72h (3d) after injury. Mice were subjected to crush of the sciatic nerve in one side, while the other nerve was spared and used as naive control condition.