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Stage-specific extracellular vesicle cargo from Schwann cells orchestrates peripheral nerve regeneration

ABSTRACT: Stage-specific extracellular vesicle cargo from Schwann cells orchestrates peripheral nerve regeneration

PROVIDER: PRJNA1281691 | ENA |

REPOSITORIES: ENA

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Stage-specific extracellular vesicle cargo from Schwann cells orchestrates peripheral nerve regeneration

Project description:Schwann cells (SCs) play a critical role in peripheral nerve regeneration, undergoing dynamic phenotype transitioning from myelinating to repair stages following injury. While SC-derived extracellular vesicles (SC-EVs) have emerged as key mediators of intercellular communication during nerve repair, their stage-specific molecular cargo and functional roles remained incomplete understood. Here, we delineate protein, microRNA and lncRNA landscapes of SC-EVs across distinct differentiation stages, including immature, myelinating, and repair phenotypes, using an in vitro model of primary rat SCs. We show that myelinating SC-EVs are enriched with reprogramming factor SOX2 and neurotrophin receptor p75NTR, while repair SC-EVs carry distinct microRNAs predicted to modulate genes involved in myelin ensheathment, neuronal differentiation and neurogenesis. Moreover, repair SC-EVs contain long non-coding RNAs (lncRNAs) that may regulate miRNA activity. These findings reveal a novel mechanism by which SC-EVs orchestrate neuronal regeneration through stage-specific molecular cargo, and establishes a foundational model for investigating SC plasticity in peripheral nerve repair

2025-07-01 | GSE300703 | GEO

Identification of extracellular vesicle miRNA cargo

Project description:Identification of extracellular vesicle miRNA cargo

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BAG6KO impacts extracellular vesicle mRNA cargo

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BAG6KO impacts extracellular vesicle mRNA cargo

Project description:The mRNA cargo of B-16V and B-16V-delta-BAG6 cells was sequenced with RNA seq.

2019-11-29 | E-MTAB-7123 | biostudies-arrayexpress

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

TFEB/3 govern repair Schwann cell generation and function following peripheral nerve injury

Project description:After peripheral nerve injury, adult Schwann cells convert to progenitor cell-like repair Schwann cells, which are pivotal for nerve regeneration. We show that Schwann cell-specific deletion of TFEB/3 disrupts the transcriptomic reprogramming necessary for injury-induced repair Schwann cell generation in mice. The mutant mice fail to generate proliferating repair Schwann cells to populate the injured nerves. Distal Schwann cells fail to express injury-responsive genes and continue to maintain the expression of myelin-associated genes. TFEB/3 binding motifs are enriched in injury-induced enhancers, suggesting their role in repair gene activation. Autophagy-dependent myelin breakdown is not impaired in the mutant mice despite the known function of TFEB/3 as autophagy activators. However, the mutant mice exhibit defects in axon regeneration, target reinnervation, and functional recovery. Therefore, TFEB/3 play a critical role in orchestrating transcriptional changes essential for repair Schwann cell generation and function necessary for peripheral nerve regeneration.

2024-08-12 | GSE249114 | GEO

Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun

Project description:After nerve injury, myelin and Remak Schwann cells reprogram to repair cells specialized for regeneration. Normally providing strong regenerative support, these cells fail in aging animals, and during the chronic denervation that results from slow axon growth. This impairs axonal regeneration and causes a significant clinical problem. We find that aging and chronically denervated repair cells express reduced c-Jun protein and the regenerative support provided by these cells is also reduced. In both cases, genetically restoring Schwann cell c-Jun levels restores regeneration to that in controls. We identify potential gene candidates mediating this effect and implicate Shh in the control of Schwann cell c-Jun levels. These experiments reveal that a common mechanism, reduced c-Jun in repair cells, underlies two major reasons for regeneration failure in the PNS. They underscore the central importance of Schwann cell c-Jun as a regulator of nerve repair, and point to molecular pathways that can be manipulated for improving the clinical outcome of nerve injuries.

2020-10-14 | E-MTAB-9640 | biostudies-arrayexpress

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

IL-22 impedes the proliferation of Schwann cells and influence nerve regeneration

Project description:Schwann cells (SCs) proliferation is crucial for axonal guidance and nerve regeneration following nerve injury. This study aims to investigate the in vitro effects of interleukin-22 (IL-22) on SCs and the corresponding mechanism.

2018-06-15 | GSE69866 | GEO

Single-cell RNA-seq reveals the difference between Schwann cells in dorsal root ganglion and sciatic nerve

Project description:Schwann cells are important glial cells in peripheral nervous system. In this study, we performed single cell RNA-sequencing (scRNA-seq) analysis of Schwann cells exist in both dorsal root ganglion(DRG) and sciatic nerve.We categorized DRG and sciatic nerve Schwann cells into different subtypes,and found common subtypes and different subtypes.In addition, we discovered the proliferation and migration ability of Schwann cells were distinct in different tissues.Our current study revealed the distinctive characteristics of Schwann cells in DRG and sciatic nerve.

2023-03-26 | GSE147615 | GEO

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