Transcriptomic analysis of proliferative or differentiated myoblasts
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE242637 | GEO | 2023/12/13
REPOSITORIES: GEO
Similar Datasets
Project description:Adult skeletal muscle is a plastic tissue that can adapt its size to workload. Here, we show that RhoA within myofibers is needed for overload-induced hypertrophy by controlling satellite cell fusion to the growing myofibers without affecting protein synthesis. At the molecular level, we demonstrate that, in response to increased workload, RhoA controls in a cell autonomous manner Erk1/2 activation and the expressions of extracellular matrix (ECM) regulators such as Mmp9/Mmp13/Adam8 and of macrophage chemo-attractants such as Ccl3/Cx3cl1. Their decreased expression in RhoA mutant is associated with ECM and fibrillar collagen disorganization and lower macrophage infiltration. Moreover, Mmps inhibition and macrophage depletion in controls phenocopied the lack of growth of RhoA mutants. These findings unravel the implication of RhoA within myofibers, in response to increase load, in the building of a permissive microenvironment for muscle growth and for satellite cell accretion through ECM remodeling and inflammatory cell recruitment.
2021-12-21 | GSE166598 | GEO
Project description:Adult skeletal muscle is a plastic tissue that can adapt its size to workload. Here, we show that RhoA within myofibers is needed for overload-induced hypertrophy by controlling satellite cell fusion to the growing myofibers without affecting protein synthesis. At the molecular level, we demonstrate that, in response to increased workload, RhoA controls in a cell autonomous manner Erk1/2 activation and the expressions of extracellular matrix (ECM) regulators such as Mmp9/Mmp13/Adam8 and of macrophage chemo-attractants such as Ccl3/Cx3cl1. Their decreased expression in RhoA mutant is associated with ECM and fibrillar collagen disorganization and lower macrophage infiltration. Moreover, Mmps inhibition and macrophage depletion in controls phenocopied the lack of growth of RhoA mutants. These findings unravel the implication of RhoA within myofibers, in response to increase load, in the building of a permissive microenvironment for muscle growth and for satellite cell accretion through ECM remodeling and inflammatory cell recruitment.
2021-12-21 | GSE166597 | GEO
Project description:Myoblast fusion is fundamental for the development of multinucleated myofibers. Evolutionarily conserved proteins required for myoblast fusion include Rac1 and its activator Dock1. Here, we tested the functions of Elmo proteins, Dock1-interacting scaffolds, on myoblast fusion. When Elmo1-/- mice underwent muscle-specific Elmo2 genetic ablation, they exhibited severe myoblast fusion defects. A mutation in the Elmo2 gene that reduced signaling resulted in a decrease in myoblast fusion. Conversely, a mutation in Elmo2 promoting its open conformation increased myoblast fusion during development and in muscle regeneration. Finally, we showed that the dystrophic features of the Dysferlin-null mice, a model of limb-girdle muscular dystrophy type 2B, were reversed when expressing Elmo2 in an open conformation. These data provide direct evidence that the myoblast fusion process could be exploited for regenerative and therapeutic purposes.
2022-07-25 | GSE209546 | GEO
Project description:Healthy skeletal muscle can regenerate after ischaemic, mechanical, or toxin-induced injury, but ageing impairs that regeneration potential. This has been largely attributed to dysfunctional satellite cells and reduced myogenic capacity. Understanding which signalling pathways are associated with reduced myogenesis and impaired muscle regeneration can provide valuable information about the mechanisms driving muscle ageing and prompt the development of new therapies. To investigate this, we developed a high-throughput in vitro model to assess muscle regeneration in chemically injured C2C12 and human myotube-derived young and aged myoblast cultures. We observed a reduced regeneration capacity of aged cells, as indicated by an attenuated recovery towards preinjury myotube size and myogenic fusion index at the end of the regeneration period, in comparison with younger muscle cells that were fully recovered. RNA-sequencing data showed significant enrichment of KEGG signalling pathways, PI3K-Akt, and downregulation of GO processes associated with muscle development, differentiation, and contraction in aged but not in young muscle cells. Data presented here suggests that repair in response to in vitro injury is impaired in aged vs. young muscle cells. Our study establishes a framework that enables further understanding of the factors underlying impaired muscle regeneration in older age.
2023-07-05 | E-MTAB-12248 | biostudies-arrayexpress
Project description:In response to skeletal muscle injury, adult myogenic stem cells, known as satellite cells, are activated and undergo proliferation and differentiation to regenerate new muscle fibers. The skeletal muscle-specific microRNA, miR-206, is up-regulated in satellite cells following muscle injury, but its role in muscle regeneration has not been defined. Here we show that skeletal muscle regeneration in response to cardiotoxin injury is impaired in mice lacking miR-206. Loss of miR-206 also accelerates and exacerbates the dystrophic phenotype of mdx mice, a model for Duchenne muscular dystrophy. MiR-206 promotes satellite cell differentiation and fusion to form multinucleated myofibers by suppressing a collection of negative regulators of myogenesis. Our findings reveal an essential role for miR-206 in satellite cell differentiation during skeletal muscle regeneration and as a modulator of Duchenne muscular dystrophy. total RNA obtained from TA muscle of mdx and 3 miR-206 KO; mdx mice at 3 months of age.
2012-04-30 | E-GEOD-36077 | biostudies-arrayexpress
Project description:Wnt/M-NM-2-catenin signaling is involved in various aspects of skeletal muscle development and regeneration. In addition, Wnt3a and M-NM-2-catenin are required for muscle-specific gene transcription in embryonic carcinoma cells and satellite-cell proliferation during adult skeletal muscle regeneration. Downstream targets of canonical Wnt signaling are cyclin D1 and c-myc. However, both target genes are suppressed during differentiation of mouse myoblast cells, C2C12. Underlying molecular mechanisms of M-NM-2-catenin signaling during myogenic differentiation remain unknown. Using C2C12 cells, we examined intracellular signaling and gene transcription during myoblast proliferation and differentiation. We confirmed that several Wnt signaling components, including Wnt9a, Sfrp2 and porcupine, were consistently upregulated in differentiating C2C12 cells. Troponin T-positive myotubes were decreased by Wnt3a overexpression, but not Wnt4. TOP/FOP reporter assays revealed that co-expression with Wnt4 reduced Wnt3a-induced luciferase activity, suggesting that Wnt4 signaling counteracted Wnt3a signaling in myoblasts. FH535, a small-molecule inhibitor of M-NM-2-catenin/Tcf complex formation, reduced basal M-NM-2-catenin in cytoplasm and decreased myoblast proliferation. K252a, a protein kinase inhibitor, increased membrane-bound M-NM-2-catenin and enhanced myoblast fusion. Treatments with K252a or Wnt4 resulted in increased cytoplasmic vesicles containing phosphorylated M-NM-2-catenin (Tyr654) during myogenic differentiation. These results suggest that various Wnt ligands control subcellular M-NM-2-catenin localization, which regulate myoblast proliferation and myotube formation. Wnt signaling via M-NM-2-catenin likely acts as a molecular switch that regulates the transition from cell proliferation to myogenic differentiation. Control cells (day 0) prior to differentiation induction with n=4; differentiated for two days with n=3; differentiated for four days with n=3.
2011-07-15 | E-GEOD-30077 | biostudies-arrayexpress
Project description:The regeneration of skeletal muscle relies on satellite cells which can proliferate, differentiate and form new myofibers upon injury. Emerging evidence suggests that misregulations of satellite cell fate and function influence the severity of Duchenne Muscular Dystrophy (DMD). The myogenic identity and maintenance of the pool of satellite cells is determined by the transcription factor PAX7. Satellite cell proliferation and self-renewal is regulated by the circadian clock. Here, we show that the CLOCK-interacting protein, Circadian (CIPC), a negative-feedback regulator of the circadian clock, is up-regulated during myoblast differentiation. Specific deletion of CIPC in satellite cells alleviated myopathy, improved muscle function and reduced fibrosis in mdx mice. CIPC deficiency led to activation of the ERK1/2 and JNK1/2 signaling pathways, which in turn activated the transcription factor SP1 to trigger the transcription of PAX7. Therefore, CIPC is a negative regulator of satellite cell function and loss of CIPC in satellite cells promotes muscle regeneration.
2022-01-27 | GSE195468 | GEO
Project description:The purpose of this study is to investigate how GDF10 regulates early myoblast differentiation and fusion. We found that melatonin can enhance fibro-adipogenic progenitors (FAPs) paracrine signaling to support muscle regeneration. Through combining transcriptome analysis and single-cell transcriptome analysis, we identified GDF10 as a type of myogenic factor specifically secreted by FAPs, which plays a beneficial role in promoting muscle fiber development and regeneration. To determine the underlying mechanism by which GDF10 regulates myogenesis, we performed RNA-seq on myoblasts treated with GDF10 or vehicle for 6 hours in vitro. We found that GDF10 promoted myoblast fusion by regulating LKB1-AMPK-MYOG-MYMK signaling during differentiation. In summary, our study revealed novel insights into the mechanism by which melatonin promotes muscle regeneration by mediating the interplay between FAPs and muscle stem cells (MuSCs).
2023-06-30 | GSE214164 | GEO
Project description:The acquisition of a proliferating cell status from a quiescent state as well as the shift between proliferation and differentiation are key developmental steps in skeletal-muscle stem cells (satellite cells) to provide proper muscle regeneration. However, how satellite-cell proliferation is regulated, though, is not fully understood. Here, we report that the c-isoform of the transcription factor Pitx2 increases cell proliferation in myoblasts by down-regulating the miRNAs miR-15b, miR-23b, miR-106b, and miR-503. This Pitx2c-miRNA pathway also regulates cell proliferation in early-activated satellite cells, enhancing the Myf5+ satellite cells and thereby promoting their commitment to a myogenic cell fate. This study reveals unknown functions of several miRNAs in myoblast and satellite-cell behaviour and thus may have future applications in regenerative medicine. mirVana microarrays (Ambion) were used to profile microRNA signature at different Pitx2 overexpression conditions, namely two different doses (4 and 8 µg CMV-Pitx2c plasmid, respectively) after 24 hours of transfection in SOL8 skeletal myogenic cells. 20 µg of total RNA was used to hybridize two distinct microRNA microarrays on each condition analyzed.
2015-06-10 | E-GEOD-53943 | biostudies-arrayexpress
Project description:In response to skeletal muscle injury, adult myogenic stem cells, known as satellite cells, are activated and undergo proliferation and differentiation to regenerate new muscle fibers. The skeletal muscle-specific microRNA, miR-206, is up-regulated in satellite cells following muscle injury, but its role in muscle regeneration has not been defined. Here we show that skeletal muscle regeneration in response to cardiotoxin injury is impaired in mice lacking miR-206. Loss of miR-206 also accelerates and exacerbates the dystrophic phenotype of mdx mice, a model for Duchenne muscular dystrophy. MiR-206 promotes satellite cell differentiation and fusion to form multinucleated myofibers by suppressing a collection of negative regulators of myogenesis. Our findings reveal an essential role for miR-206 in satellite cell differentiation during skeletal muscle regeneration and as a modulator of Duchenne muscular dystrophy.
2012-05-01 | GSE36077 | GEO