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: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.
Project description:ChIP-seq of H3K27me3 in rat peripheral nerve was used to identify sites of polycomb repression associated with genes in Schwann cells, which constitute the majority of cells in peripheral nerve. H3K27me3 ChIP samples were prepared from rat sciatic nerve and then sequenced. Inputs for these ChIP samples have previously been submitted as samples GSM1541282 and GSM1541283 in Series GSE63103
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:ChIP-seq of H3K27me3 in rat peripheral nerve was used to identify sites of polycomb repression associated with genes in Schwann cells, which constitute the majority of cells in peripheral nerve.
Project description:Peripheral nerves provide a supportive growth environment for developing and regenerating axons and are essential for maintenance and repair of many non-neural tissues. This capacity has largely been ascribed to paracrine factors secreted by nerve-resident Schwann cells. Here, we used single-cell transcriptional profiling to identify ligands made by different injured rodent nerve cell types and have combined this with cell-surface mass spectrometry to computationally model potential paracrine interactions with peripheral neurons. These analyses show that peripheral nerves make many ligands predicted to act on peripheral and CNS neurons, including known and previously uncharacterized ligands. While Schwann cells are an important ligand source within injured nerves, more than half of the predicted ligands are made by nerve-resident mesenchymal cells, including the endoneurial cells most closely associated with peripheral axons. At least three of these mesenchymal ligands, ANGPT1, CCL11, and VEGFC, promote growth when locally applied on sympathetic axons. These data therefore identify an unexpected paracrine role for nerve mesenchymal cells and suggest that multiple cell types contribute to creating a highly pro-growth environment for peripheral axons.
Project description:The striking PNS regenerative response to injury rests on the plasticity of adult Schwann cells and their ability to transit between differentiation states, a highly unusual feature in mammals. Using mice with inactivation of Schwann cell c-Jun, we show that the injury response involves c-Jun dependent natural reprograming of differentiated cells to generate a distinct Schwann cell state specialized to promote regeneration. Transected distal stumps of c-Jun mutants show 172 disregulated genes, resulting in abnormal expression of growth factors, adhesion molecules and cytoskeletal changes that lead to neuronal death, inhibition of axon growth and striking failures of functional repair after injury. These observations provide a molecular basis for understanding Schwann cell plasticity and nerve regeneration. They offer conclusive support for the notion that Schwann cells control repair in the PNS, using dedicated transcriptional controls to generate a distinct repair cell, a transition that shows similarities to transdifferentiation seen in other systems. Total RNA was purified from a 10mm segment of the distal stump and uninjured contralateral nerve from c-Jun mutants and control mice 7 days after nerve cut. For each condition (injured/uninjured) and genotype (control/ knock-out) 2 independent samples (replicates) were generated from pooled nerves of 4/6 mice resulting in a total of 8 samples: CTRL.cut.R1, CTRL.cut.R2, CTRL.uncut.R1, CTRL.uncut.R2, KO.cut.R1, KO.cut.R2, KO.uncut.R1,KO.uncut.R2.