Myf6/MRF4 Mediated Myokine Signaling is Required for the Maintenance of the Adult Skeletal Muscle Stem Cell Pool
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA510349 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8329190.fastq.gz | Fastqsanger.gz | |||
| SRR8329191.fastq.gz | Fastqsanger.gz | |||
| SRR8329192.fastq.gz | Fastqsanger.gz | |||
| SRR8329193.fastq.gz | Fastqsanger.gz | |||
| SRR8329194.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 14 |
Similar Datasets
Project description:In metazoans, skeletal muscle evolved to contract and to produce force. Recent experimental evidence suggests, however, that skeletal muscle has also acquired endocrine functions and produces a vast array of myokines, but how myokine production is regulated and how they affect the resident stem cell population of the skeletal muscle is unknown. Here, we show that in adult skeletal muscle, Myf6/MRF4 is a major regulator of myokine expression. Genetic deletion of Myf6 in skeletal muscles leads to exhaustion of the muscle stem cell (MuSCs) pool in adult mice in a myokine-dependent manner but, surprisingly, does not disrupt muscle differentiation. Using ChIP-Seq and gene expression analyses of myogenic factors, we show that Myf6/MRF4 is essential for the transcriptional activation of many myokines and muscle-secreted proteins, including ligands for canonical signaling pathways such as EGFR, VEGFR and STAT3. Consequently, MuSCs from Myf6 knockout animals show impaired activation of those signaling pathways and exhibit impaired quiescence, defective self-renewal, but nevertheless undergo differentiation. Lastly, we show that induction of myokine expression during aerobic and anaerobic exercise closely correlates with Myf6 expression. Together, these findings indicate that control of myokine signaling by Myf6 is critical to maintain muscle stem cell pool in adult skeletal muscle.
2020-09-18 | GSE123836 | GEO
Project description:Mitochondria play a central role in muscle metabolism and function. In skeletal muscles, a unique family of iron-sulfur proteins, termed CISD proteins, support mitochondrial function. The level of these proteins declines with age leading to muscle degeneration. Although the function of the outer mitochondrial proteins CISD1 and CISD2 was defined, the role of the inner mitochondrial protein CISD3, is currently unknown. Here we show that CISD3 deficiency in mice results in muscle atrophy that shares proteomic features with Duchenne Muscular Dystrophy. We further reveal that CISD3 deficiency impairs the function and structure of skeletal muscle mitochondria, and that CISD3 interacts with, and donates its clusters to, Complex I respiratory chain subunit NDUFV2. These findings reveal that CISD3 is important for supporting the biogenesis and function of Complex I, essential for muscle maintenance and function. Interventions that target CISD3 could therefore impact muscle degeneration syndromes, aging, and related conditions.
2024-05-07 | PXD042593 | Pride
Project description:In metazoans, skeletal muscle evolved to contract and produce force. Recent experimental evidence, however, suggests that skeletal muscle has also acquired endocrine functions and produces a vast array of muscle-derived cytokines and growth factors, collectively called myokines. The mechanisms that regulate myokine production and their effect on the resident stem cell population inskeletal muscle remain unknown. Here, we report that in adult skeletal muscle, Myf6/MRF4 is a major regulator of myokine expression. Genetic deletion of Myf6 in skeletal muscle leads to reduction of the muscle stem cell (MuSCs) pool in adult mice in a myokine-dependent manner but, surprisingly, does not disrupt muscle differentiation. Using ChIP-Seq and gene expression analyses of myogenic factors, we show that Myf6/MRF4 is a direct regulator of many myokines and muscle-secreted proteins, including ligands for canonical signaling pathways such as EGFR and VEGFR. Consequently, in Myf6-deficient animals,MuSCs increasingly break quiescence, but can nevertheless undergo differentiation. Lastly, we show that Myf6 and its gene network rapidly respondto aerobic and anaerobic exercise. Together, these findings indicate that control of myokine signaling by Myf6 is critical to maintain muscle stem cell pool and skeletal muscle function via myokine signaling.
2020-10-02 | GSE133505 | GEO
Project description:In recent years, aromatherapy for sportspersons termed as sports aromatherapy has been attracting attention in the field of sports, and aromatic baths and aromatherapy treatments are being used as a new conditioning method, mainly by athletes. Among these, aroma treatment is used to improve performance and recovery from fatigue. On the other hand, myokines (muscle-derived cytokines and chemokines) secreted from the skeletal muscles after exercise, have recently been attracting attention. Many types of myokines are known to act on various organelles and through diverse beneficial metabolic actions promote health. One of them is IL-6, which has been reported to act on muscles and promote myogenesis. Previous studies on essential oil treatment effects are thought to be due to aroma or massage stimulation, and there are no reports of direct effects on muscle at the molecular level comparing essential oils with carrier oils alone. Therefore, we aimed to elucidate the molecular mechanism of myokine secretion by the addition of an essential oil (Lavender oil, LO) using an in vivo exercise model of a mouse muscle cell line (C2C12 cells), which are known as exercise cells.
2024-08-30 | GSE273992 | GEO
Project description:Maintenance and self-renewal of the spermatogonial stem cell (SSC) population is the cornerstone of male fertility. In this manuscript we have identified a key role for the nucleosome remodelling protein Chromodomain Helicase DNA binding protein 4 (CHD4) in regulating SSC function. Gene expression analyses revealed that CHD4 expression is largely restricted to spermatogonia in the mouse testis, and is particularly enriched in SSCs. Using spermatogonial transplantation techniques and RNAi mediated knockdown it was established that loss of Chd4 expression significantly impairs SSC regenerative capacity, resulting in a ~50% reduction in colonisation of recipient testes. A single cell RNA-seq comparison depicted reduced expression of ‘self-renewal’ genes such as Gfra1 and Pten following Chd4 knockdown, along with increased expression of signature progenitor genes, Neurog3 and Dazl. Co-immunoprecipitation analyses demonstrated that CHD4 regulates gene expression in spermatogonia not only though its traditional association with the remodelling complex NuRD, but also via interaction with the GDNF-responsive transcription factor SALL4. Cumulatively, the results of this study depict a previously unappreciated fundamental role for CHD4 in controlling fate decisions in the spermatogonial pool.
2021-06-17 | PXD022066 | Pride
Project description:Cachexia is associated with poor prognosis in patients with chronic heart failure. The underlying mechanisms of cachexia triggered heart failure progression, however, are not well understood. Here, we investigated whether the dysregulation of myokine expression from wasting skeletal muscle and impaired inter-organ crosstalk during advanced heart failure might contribute to progression of the disease. RNA sequencing analysis from wasting skeletal muscles of mice with cardiac cachexia during long-term pressure overload revealed a strongly reduced expression of Ostn. Ostn encodes for the skeletal muscle derived myokine Musclin, which had been previously implicated in the enhancement of natriuretic peptide (NP) signaling. Using newly developed skeletal muscle specific, inducible Ostn knock-out mice, we demonstrated that reduced skeletal muscle Musclin levels exaggerated cardiac dysfunction and myocardial fibrosis compared to littermate control mice after TAC. Restoration of Musclin deficiency during cardiac cachexia via AAV6-mediated skeletal muscle specific Musclin overexpression, in turn, attenuated left ventricular dysfunction and myocardial fibrosis. Mechanistically, we found that Musclin enhanced CNP/NPR2/cGMP signaling in cardiomyocytes, which led to improved contractility by inhibition of the cAMP degrading phosphodiesterase (PDE)3 and augmented cAMP/protein kinase A signaling. In addition, Musclin directly acted on cardiac fibroblasts to inhibit their activation. Together, our study indicates the therapeutic potential of targeting interorgan cross-talk during heart failure, for example by counteracting the impaired secretion of the Musclin from wasting skeletal muscle.
2021-11-02 | GSE129205 | GEO
Project description:Our results demonstrate that targeted deletion of TAK1 inhibits muscle growth during post-natal development period. Inactivation of TAK1 also causes muscle wasting in adult mice. TAK1 regulates expression of a number of molecules and signaling pathways which mediate growth and maintenance of skeletal muscle.
2018-02-28 | GSE104586 | GEO
Project description:TAK1 is essential for growth and maintenance of skeletal muscle mass
| PRJNA413137 | ENA
Project description:In this study, we show that muscle-specific inactivation of FBXW7 elicits striking defects in postprandial glucose metabolism and failure to maintain skeletal muscle mass in adult mice. Further, mice lacking FBXW7 exhibited impaired endurance capacity and exacerbated HFD-induced insulin resistance and postprandial hyperglycemia. At the mechanistic level, RNAseq and quantitative proteomic analysis revealed global effects of FBXW7 deficiency on skeletal muscle transcriptome and proteome. This work illustrates a prominent role of FBXW7 in integrating postprandial nutritional signals to coordinate glucose metabolism and muscle mass maintenance.
2024-06-21 | GSE140503 | GEO
Project description:A regulatory role for CHD4 in maintenance of the spermatogonial stem cell pool
| PRJNA684464 | ENA