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E-MTAB-5633

ABSTRACT: Changes in the coding/non-coding transcriptome and DNA methylome that define the Schwann cell repair phenotype after nerve injury

PROVIDER: E-MTAB-5633 | ExpressionAtlas | 2019-05-14

REPOSITORIES: ExpressionAtlas

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Changes in the coding/non-coding transcriptome and DNA methylome that define the Schwann cell repair phenotype after nerve injury

Project description:Changes in the coding/non-coding transcriptome and DNA methylome that define the Schwann cell repair phenotype after nerve injury

| PRJEB20165 | ENA

Changes in the coding/non-coding transcriptome and DNA methylome that define the Schwann cell repair phenotype after nerve injury

Project description:Schwann cell (Büngner) repair cells play a critical role in orchestrating nerve repair after injury, but the reprogramming process that generates them is poorly understood. We present the first combined whole genome coding and non-coding RNA and CpG methylation study after nerve injury. We show that genes involved in epithelial to mesenchymal transition are enriched in repair cells and we identify long non-coding RNAs in Schwann cells. We demonstrate that the AP-1 transcription factor c-Jun regulates the expression of certain micro RNAs in repair cells, in particular miR-21 and miR-34. Surprisingly, changes in CpG methylation are limited in injury, unlike development, and restricted to specific locations, such as enhancer regions of novel Schwann cell specific genes, such as Nedd4l, and near to local enrichment of AP-1 motifs. These epigenetic changes significantly broaden our understanding of Schwann cell reprogramming in peripheral nervous system tissue repair. To identify epigenetic regulators underlying successful nerve regeneration we generated RNA-Seq, small-RNA-Seq and whole genome bisulfite sequencing libraries for uninjured nerve versus three and/or seven day post nerve transection sciatic nerves of adult C57BL/6J mice crush.

2017-08-30 | E-MTAB-5633 | biostudies-arrayexpress

Promoting axon regeneration by enhancing the non-coding function of the injury-responsive coding gene Gpr151

Project description:Gene expression profiling in response to nerve injury has been mainly focused on protein functions of coding genes to understand mechanisms of axon regeneration and to identify targets of potential therapeutics for nerve repair. However, the protein functions of several highly injury-induced genes including Gpr151 for regulating the regenerative ability remain unclear. Here we present an alternative approach focused on non-coding functions of the coding genes, which led to the identification of the non-coding function of Gpr151 RNA interacting with RNA-binding proteins such as CSDE1. Gpr151 promotes axon regeneration by the function of its 5’- untranslated region (5’UTR) and expression of an engineered form of the 5’UTR improves regenerative capacity in vitro and in vivo in both sciatic nerve and optic nerve injury models. Our data suggest that searching injury-induced coding genes potentially functioning by their non-coding regions is required for the RNA-based gene therapy for improving axon regeneration.

2021-07-01 | GSE179145 | GEO

FOSL1 modulates Schwann cell responses in the wound microenvironment and regulates peripheral nerve regeneration

Project description:Peripheral glial Schwann cells switch to a repair state after nerve injury, proliferate to supply lost cell population, migrate to form regeneration tracks, and generates a permissive microenvironment for nerve regeneration. Exploring essential regulators of the repair responses of Schwann cells may benefit the clinical treatment for peripheral nerve injury. In the present study, FOSL1 regulates Schwann cell phenotype modulation and provided a novel therapeutic approach to orchestrate the regeneration and functional recovery of injured peripheral nerves.

2022-10-02 | GSE214449 | GEO

Temporal Changes in Macrophage Phenotype after Peripheral Nerve Injury

Project description:Temporal Changes in Macrophage Phenotype after Peripheral Nerve Injury

| PRJNA417027 | ENA

Gene expression data from human primary cultured Schwann cells

Project description:Schwann cells undergo reprogramming after nerve injury, switching to immature repair phenotype. The goal was to test what genetic perturbations are triggered in Schwann cells with the stimulus from melanoma cell secreted factors. We used microarrays to detail the changes in gene expression of Schwann cells treated with human melanoma conditioned medium.

2019-02-05 | GSE126040 | 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

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

2017-11-21 | GSE107180 | GEO

c-JUN REPROGRAMS SCHWANN CELLS OF INJURED NERVES TO GENERATE A REPAIR CELL ESSENTIAL FOR REGENERATION

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.

2012-06-13 | E-GEOD-38693 | biostudies-arrayexpress

Sciatic nerve injury-responsive differential mRNA profile and ribosome association efficiency of injury-induced mRNA

Project description:After nerve injury in the pheripheral nervous system, axon regeneration occurs through transcriptomic changes in neuronal cell bodies. To investigate which protein-coding transcripts are up-regulated and directed to ribosomes or not, we used RiboTag+/+;Advillin-Cre+ mice, expressing HA-tagged RPL22 specifically in sensory neurons, to profile their ribosome binding RNAs in nerve injured or uninjured dorsal root ganglion(DRG) tissues using HA-IP sequencing. We analyzed the results together with total RNA transcriptomics conducted under the same conditions. Through this analysis, we found mRNA of Gpr151 gene, one of the transcript that highly responds to injury but does not direct to the ribosomes, promoting axon regeneration by a non-coding RNA function.

2023-08-18 | GSE237046 | GEO

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