Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA357461 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This project aimed to assess the role of pharmacological inhibition of the aryl hydrocarbon receptor (AhR) on skeletal muscle and cortical bone health in aged mice. As part of a broader systems biology approach, proteomic profiling was employed to investigate molecular mediators of neuromuscular junction (NMJ) function in skeletal muscle tissue. The study compared vehicle-treated versus BAY2416964-treated aged mice, revealing key differentially expressed proteins involved in axonal development and NMJ stability.
2025-07-06 | PXD065529 | Pride
Project description:Embryonic mouse diaphragm is a primary model for studying myogenesis and neuro-muscular synaptogenesis, both of which represent processes regulated by spatially organized genetic programs of myonuclei located in distinct myodomains. However, a spatial gene expression pattern of embryonic mouse diaphragm has not been reported. Here we provide spatially resolved gene expression data for horizontally sectioned embryonic mouse diaphragms at E14.5 and E18.5. These data reveal gene signatures for specific muscle regions with distinct maturity and fiber type composition, as well as for a central neuromuscular junction and a peripheral myotendinous junction compartments. Comparing spatial expression patterns of wild type mice with those of mouse mutants lacking either the skeletal muscle calcium channel CaV1.1 or b-catenin, reveals curtailed muscle development and dysregulated expression of genes potentially involved in NMJ formation. Altogether, these datasets provide a powerful recourse for further studies of muscle development and NMJ formation in the mouse embryo.
2024-05-23 | GSE244014 | 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:X-linked Spinal and Bulbar Muscular Atrophy (SBMA) is a rare, late-onset neuromuscular disease caused by a CAG repeat expansion mutation in the androgen receptor (AR) gene. SBMA is characterized by progressive muscle atrophy of both neurogenic and myopathic etiologies. Previous work has established that mutant AR expression in skeletal muscle could be a significant contributor to neuromuscular decline, yet the mechanisms involved remain ill-defined. As AR is a nuclear hormone receptor transcription factor, we sought to define early changes in gene expression in skeletal muscle of pre-symptomatic SBMA mice, with a focus on transcriptional changes at the neuromuscular junction (NMJ). We describe loss of key NMJ-specific genes in synaptic muscle regions of pre-symptomatic SBMA mice, while extrasynaptic muscle features a coordinated loss of sarcomere genes that coincides with ectopic re-expression of certain NMJ genes. Furthermore, SBMA muscle prominently features dysregulated calcium flux, likely stemming from a compensatory response to early atrophy that greatly exacerbates over time. The SERCA activator CDN1163 conferred a mild rescue in function and muscle size in SBMA mice, while genetic deletion of the gene encoding Myf6/MRF4, a negative regulator of sarcomere gene expression and predicted AR interactor, did not ameliorate muscle atrophy. These studies suggest that modulation of calcium flux could be a promising pharmacological target in SBMA.
2025-05-16 | GSE296707 | GEO
Project description:The development and maintenance of the neuromuscular junction (NMJ) requires reciprocal signals between the nerve terminals and the multinucleate skeletal muscle fiber (myofiber). This interaction leads to highly specialized transcription in the sub-synaptic or NMJ myonuclei within mature myofibers leading to clustering of acetylcholine receptors (AChRs). Here we utilized single-nucleus RNA sequencing (snRNA-seq) to delineate the transcriptional response of myonuclei to denervation. Through snRNA-seq on skeletal muscle from two independent mouse models of denervation, sciatic nerve transection and amyotrophic lateral sclerosis, we identify a multimodal transcriptional response of NMJ-enriched genes and an alteration in cholesterol homeostasis in both slow and fast myofibers. Gramd1, a family of genes involved in non-vesicular cholesterol transport, are enriched at the NMJ at baseline and upregulated in both models of denervation by the NMJ and extrasynaptic myonuclei In vivo gain and loss of function studies indicate that NMJ-enriched Gramd1 genes regulate myofiber sizes independent of an obvious impact on AChR clustering. We uncovered a dynamic transcriptional response of myonuclei to denervation and highlight a critical role for cholesterol transport to maintain myofiber sizes.
2025-09-08 | GSE279996 | GEO
Project description:The neuromuscular junction (NMJ) is the synapse formed between motor neurons and skeletal muscle fibers. Its stability relies on the continued expression of genes in a subset of myonuclei, called NMJ myonuclei. Here, we use single-nuclei RNA-sequencing (snRNA-seq) to identify numerous undescribed NMJ-specific transcripts. To elucidate how the NMJ transcriptome is regulated, we also performed snRNA-seq on sciatic nerve transected, botulinum toxin injected and Musk knockout muscles. These data show that NMJ gene expression is not only driven by agrin-Lrp4/MuSK signaling, but is also affected by electrical activity and trophic factors other than agrin. By selecting three previously undescribed NMJ genes Etv4, Lrtm1 and Pdzrn4, we further characterize novel contributors to NMJ stability and function. AAV-mediated overexpression and AAV-CRISPR/Cas9-mediated knockout show that Etv4 is sufficient to upregulate expression of ~50% of the NMJ genes in non-synaptic myonuclei, while muscle-specific knockout of Pdzrn4 induces NMJ fragmentation. Further investigation of Pdzrn4 revealed that it localizes to the Golgi apparatus and interacts with MuSK protein. Collectively, our data provide a rich resource of NMJ transcripts, highlight the importance of ETS transcription factors at the NMJ and suggest a novel pathway for NMJ post-translational modifications.
2025-02-10 | GSE267910 | GEO
Project description:The neuromuscular junction (NMJ) is the synapse formed between motor neurons and skeletal muscle fibers. Its stability relies on the continued expression of genes in a subset of myonuclei, called NMJ myonuclei. Here, we use single-nuclei RNA-sequencing (snRNA-seq) to identify numerous undescribed NMJ-specific transcripts. To elucidate how the NMJ transcriptome is regulated, we also performed snRNA-seq on sciatic nerve transected, botulinum toxin injected and Musk knockout muscles. These data show that NMJ gene expression is not only driven by agrin-Lrp4/MuSK signaling, but is also affected by electrical activity and trophic factors other than agrin. By selecting three previously undescribed NMJ genes Etv4, Lrtm1 and Pdzrn4, we further characterize novel contributors to NMJ stability and function. AAV-mediated overexpression and AAV-CRISPR/Cas9-mediated knockout show that Etv4 is sufficient to upregulate expression of ~50% of the NMJ genes in non-synaptic myonuclei, while muscle-specific knockout of Pdzrn4 induces NMJ fragmentation. Further investigation of Pdzrn4 revealed that it localizes to the Golgi apparatus and interacts with MuSK protein. Collectively, our data provide a rich resource of NMJ transcripts, highlight the importance of ETS transcription factors at the NMJ and suggest a novel pathway for NMJ post-translational modifications.
2025-02-10 | GSE267909 | GEO
Project description:Poor skeletal muscle fitness contributes to many chronic disease states including obesity, heart failure, primary muscle disorders, and age-related sarcopenia. Receptor Interacting Protein 140 (RIP140) is a striated muscle-enriched nuclear receptor co-regulator. To investigate the role of RIP140 in skeletal muscle, striated muscle-specific RIP140-deficient (strNrip1-/-) mice were generated and characterized. strNrip1-/- mice display a remarkable endurance performance phenotype based on endurance treadmill performance, VO2max testing, and functional assessment of isolated muscle. RNA-sequence analysis of glycolytic fast-twitch muscle from the strNrip1-/- mice identified a broad array of differentially upregulated metabolic and structural muscle genes involved in muscle endurance fitness pathways including mitochondrial biogenesis and respiration, fatty acid oxidation, triglyceride dynamics, muscle fiber type, angiogenesis, and neuromuscular junction (NMJ) remodeling. Assessment of the structural correlates of these processes confirmed the function of RIP140 as placing a “brake” on the transcriptional network controlling these key muscle endurance fitness processes. Integration of the RNA sequence results with CUT&RUN analysis of strNrip1-/- myotubes identified direct RIP140 targets including genes involved in fatty acid metabolism and NMJ biogenesis. We conclude that RIP140 serves as a physiological “rheostat” for a broad network of genes involved in skeletal muscle fitness.
2025-08-27 | GSE289569 | GEO
Project description:Poor skeletal muscle fitness contributes to many chronic disease states including obesity, heart failure, primary muscle disorders, and age-related sarcopenia. Receptor Interacting Protein 140 (RIP140) is a striated muscle-enriched nuclear receptor co-regulator. To investigate the role of RIP140 in skeletal muscle, striated muscle-specific RIP140-deficient (strNrip1-/-) mice were generated and characterized. strNrip1-/- mice display a remarkable endurance performance phenotype based on endurance treadmill performance, VO2max testing, and functional assessment of isolated muscle. RNA-sequence analysis of glycolytic fast-twitch muscle from the strNrip1-/- mice identified a broad array of differentially upregulated metabolic and structural muscle genes involved in muscle endurance fitness pathways including mitochondrial biogenesis and respiration, fatty acid oxidation, triglyceride dynamics, muscle fiber type, angiogenesis, and neuromuscular junction (NMJ) remodeling. Assessment of the structural correlates of these processes confirmed the function of RIP140 as placing a “brake” on the transcriptional network controlling these key muscle endurance fitness processes. Integration of the RNA sequence results with CUT&RUN analysis of strNrip1-/- myotubes identified direct RIP140 targets including genes involved in fatty acid metabolism and NMJ biogenesis. We conclude that RIP140 serves as a physiological “rheostat” for a broad network of genes involved in skeletal muscle fitness.
2025-08-27 | GSE289567 | GEO
Project description:Poor skeletal muscle fitness contributes to many chronic disease states including obesity, heart failure, primary muscle disorders, and age-related sarcopenia. Receptor Interacting Protein 140 (RIP140) is a striated muscle-enriched nuclear receptor co-regulator. To investigate the role of RIP140 in skeletal muscle, striated muscle-specific RIP140-deficient (strNrip1-/-) mice were generated and characterized. strNrip1-/- mice display a remarkable endurance performance phenotype based on endurance treadmill performance, VO2max testing, and functional assessment of isolated muscle. RNA-sequence analysis of glycolytic fast-twitch muscle from the strNrip1-/- mice identified a broad array of differentially upregulated metabolic and structural muscle genes involved in muscle endurance fitness pathways including mitochondrial biogenesis and respiration, fatty acid oxidation, triglyceride dynamics, muscle fiber type, angiogenesis, and neuromuscular junction (NMJ) remodeling. Assessment of the structural correlates of these processes confirmed the function of RIP140 as placing a “brake” on the transcriptional network controlling these key muscle endurance fitness processes. Integration of the RNA sequence results with CUT&RUN analysis of strNrip1-/- myotubes identified direct RIP140 targets including genes involved in fatty acid metabolism and NMJ biogenesis. We conclude that RIP140 serves as a physiological “rheostat” for a broad network of genes involved in skeletal muscle fitness.
2025-08-27 | GSE289576 | GEO