Transcriptome analysis of neuromuscular junction during degeneration and regeneration of axon terminal
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB20663 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR1954470.fastq.gz | Fastqsanger.gz | |||
| ERR1954471.fastq.gz | Fastqsanger.gz | |||
| ERR1954472.fastq.gz | Fastqsanger.gz | |||
| ERR1954473.fastq.gz | Fastqsanger.gz | |||
| ERR1954474.fastq.gz | Fastqsanger.gz |
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Project description:The neuromuscular junction (NMJ) is a specialized tripartite synapse composed of the motor axon terminal, covered by perisynaptic Schwann cells (PSCs), and the muscle fibre, separated by a basal lamina. It is exposed to different kind of injures such as mechanical traumas, pathogens including neurotoxins, and neuromuscular diseases such as amyotrophic lateral sclerosis and immune-mediated disorders, and has retained throughout vertebrate evolution an intrinsic ability for repair and regeneration, at variance from central synapses1. Following peripheral nerve injury, an intense but poorly defined crosstalk takes place at the NMJ among its components, functional to nerve terminal regeneration. To identify crucial factors released by PSCs and the muscle to induce nerve regrowth, we performed a transcriptome analysis of the NMJ at different time points after injection of -latrotoxin, a presynaptic neurotoxin isolated from the venom of the black widow spider. This toxin is a simple and controlled method to induce an acute, localized and reversible nerve terminal degeneration not blurred by inflammation, and can help to identify molecules involved in the intra- and inter-cellular signalling governing NMJ regeneration.
2017-05-30 | E-MTAB-5730 | biostudies-arrayexpress
Project description:Understanding neuromuscular junction (NMJ) repair mechanisms is essential for addressing degenerative neuromuscular conditions. Here, we focus on the role of muscle-resident Schwann cells in NMJ reinnervation. Using an accepted model of progressive NMJ degeneration, Sod1-/- mice, we identified a clear NMJ ‘regenerative window’ that allowed us to define cellular and molecular regulators of synapse remodeling and muscle fiber reinnervation. High-resolution imaging and single-cell RNA sequencing provide a detailed analysis of Schwann cell number, morphology, and transcriptome revealing multiple subtypes, including a previously unrecognized terminal Schwann cell (tSC) population expressing a synapse promoting signature. We also discovered a novel SPP1-driven cellular interaction between myelin Schwann cells and tSCs and show that it promotes tSC proliferation and reinnervation following nerve injury in wild type mice. Our findings offer important insights into molecular regulators critical in NMJ reinnervation that are mediated through tSCs to maintain NMJ function.
2024-11-02 | GSE246865 | GEO
Project description:Understanding neuromuscular junction (NMJ) repair mechanisms is essential for addressing degenerative neuromuscular conditions. Here, we focus on the role of muscle-resident Schwann cells in NMJ reinnervation. Using an accepted model of progressive NMJ degeneration, Sod1-/- mice, we identified a clear NMJ regenerative window that allowed us to define cellular and molecular regulators of synapse remodeling and muscle fiber reinnervation. High-resolution imaging and single-cell RNA sequencing provide a detailed analysis of Schwann cell number, morphology, and transcriptome revealing multiple subtypes, including a previously unrecognized terminal Schwann cell (tSC) population expressing a synapse promoting signature. We also discovered a novel SPP1-driven cellular interaction between myelin Schwann cells and tSCs and show that it promotes tSC proliferation and reinnervation following nerve injury in wild type mice. Our findings offer important insights into molecular regulators critical in NMJ reinnervation that are mediated through tSCs to maintain NMJ function.
2025-12-09 | GSE311353 | GEO
Project description:Muscle fibroadipogenic progenitor (FAP) cells, which are muscular mesenchymal cells that originate from lateral plate mesoderm have been proposed to act as a critical regulator for adult muscle homeostasis1–7, including the maturation and proper functioning of the neuromuscular junction (NMJ)3, Prx-Bap1 paper. However, the mechanism and intercellular crosstalk by which FAPs regulate the stability and functionality of neuromuscular system remains unknown. Here we show that FAPs not only locally but also systemically regulate the neuromuscular system through the secretion of a serine-type endopeptidase Granzyme E which may imply the previously unidentified endocrine function of FAPs. Local transplantation of wild-type FAPs into the neuromuscular disease model (Prrx1Cre;Bap1f/f, hereafter, cKO) can readily prevent neuromuscular defects, including degeneration of the neuromuscular junction and loss of motor neurons. These effects are found not only in transplanted hindlimb muscles but also in the contralateral hindlimb and even forelimb muscles. Notably, subcutaneous administration of microparticles encapsulating FAP-conditioned media into cKO mice was sufficient to restore normal neuromuscular functions. By analyzing the transcriptomic and secretomic profiles of FAPs, we identified a novel protein, Granzyme E, which is specifically expressed in and secreted by FAPs, and which indispensably regulates the structure and function of NMJ and motor neuron survival. Our study has defined a unique mechanism of Granzyme E-dependent, systemic control of the neuromuscular system by FAPs, which would provide a comprehensive understanding on the neuromuscular systems and their crosstalk with non-neuronal cells. These findings may provide a therapeutic benefit to treat NMJ-related diseases.
2022-08-31 | GSE199660 | GEO
Project description:During aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume and function, which is often associated with denervation and a loss of muscle stem cells (MuSCs). A relationship between MuSCs and innervation has not been established however. Herein, we administered neuromuscular trauma to a MuSC lineage tracing model and observed a subset of MuSCs specifically engraft in a position proximal to the neuromuscular junction (NMJ). In aging and in a model of neuromuscular degeneration (Sod1-/-), this localized engraftment behavior was reduced. Genetic rescue of motor neurons in Sod1-/- mice reestablished integrity of the NMJ and partially restored MuSC ability to engraft into NMJ proximal positions. Using single cell RNA-sequencing of MuSCs, we demonstrate that a subset of MuSCs are molecularly distinguishable from MuSCs responding to myofiber injury. These data reveal unique features of MuSCs that respond to synaptic perturbations caused by aging and other stressors.
2021-05-06 | GSE165978 | GEO
Project description:This investigation leverages single-cell RNA sequencing (scRNA-Seq) to delineate the contributions of muscle-resident Schwann cells to neuromuscular junction (NMJ) remodeling in models of healthy, partially denervated, and completely denervated muscles. The study identifies several distinct Schwann cell subtypes, notably a novel terminal Schwann cell (tSC) subtype integral to the denervation-reinnervation cycle, distinguished by a transcriptomic signature indicative of cell migration and polarization. It also characterizes three myelin Schwann cell subtypes, which are notably enriched with genes associated with myelin production, in addition to mesenchymal differentiation and collagen synthesis. Importantly, SPP1 signaling emerges as a pivotal regulator of NMJ dynamics, promoting Schwann cell proliferation and muscle reinnervation across the studied nerve injury models. These findings advance our understanding of NMJ maintenance and regeneration and underscore the therapeutic potential of targeting specific molecular pathways to treat neuromuscular and neurodegenerative disorders.
2025-03-12 | GSE291457 | GEO
Project description:Regeneration of the neuromuscular junction (NMJ) is orchestrated by signals exchanged among its components. Neuronal hydrogen peroxide (H2O2), produced in response to injury, is a major Schwann cells (SC) activator. Genes differentially expressed by SCs exposed to H2O2 were used as a signature gene set for functional enrichment analysis of NMJ transcripts profiled during motor axon terminal degeneration and re-growth. We found that at the regenerating NMJ: i) the H2O2 signature is enriched in extracellular matrix terms; ii) the mRNA of Connective Tissue Growth Factor (Ctgf) is strongly up-regulated, iii) Ctgf is produced by terminal SCs, iv) Ctgf neutralization delays functional recovery upon nerve injury. We show here compelling evidence of a pro-regenerative role of Ctgf in neurotransmission rescue, and that the transcriptome of the regenerating NMJ is a powerful source of candidates with pro-regenerative potential. A profound ECM remodeling occurs during nerve regeneration, and H2O2 is among the triggers.
2023-01-04 | GSE154547 | GEO
Project description:Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition resulting from the toxic action of cancer therapies on peripheral neurons. CIPN features axon terminal retraction from target organs leading to a myriad of sensory symptoms such as mechanical and thermal insensitivity, tingling, numbness and burning pain. There are currently no preventative or curative treatments, mostly because the mechanisms leading to axon degeneration upon chemotherapy treatment in humans remain largely unknown. We developed a model of CIPN suitable for high-throughput screening that involves progressive axon degeneration culminating in the death of human iPSC-derived sensory neurons exposed to paclitaxel. Using this model, we screened a library of 192 kinase inhibitors and identified 19 neuroprotective compounds. The top neuroprotective compounds all inhibited members of the STE20 family of kinases; MAP4K4, MAP4K6, and MAP4K7. Genetic and pharmacological inhibition confirmed that simultaneous, but not individual, inhibition of these three kinases is necessary for protection against paclitaxel-induced axonal toxicity in our model, and also in human primary DRG neurons. Importantly, pharmacological inhibitors specific to the STE20 family of kinases did not prevent paclitaxel-mediated killing of three breast cancer cell lines. Transcriptomic studies revealed that it was inhibition of the JNK-c-Jun pathway that prevented cell death and inhibition of the MAP4K-p38 axis that rescued axon degeneration. STE20 kinases are, therefore, a potential therapeutic target for mitigating paclitaxel-induced axon degeneration in sensory neurons while maintaining the therapeutic effects of chemotherapy in cancer patients.
2025-10-17 | GSE298389 | GEO
Project description:Temporal transcriptomics of human 3D neuromuscular cultures reveal key signatures of neuromuscular junction development
| PRJNA1266181 | ENA
Project description:NMJ Junction various time points normal C57BL10 LCM mRNA Keywords: other
2005-03-10 | GSE2394 | GEO