Large Maf Transcription Factors Reawaken Evolutionarily Dormant Fast-Glycolytic Type IIb Myofibers in Human Skeletal Muscle
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PROVIDER: PRJNA1195913 | ENA |
REPOSITORIES: ENA
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Project description:Small mammals, such as mice, rely on the rapid contraction of skeletal muscles to achieve swift movements. These capabilities are enabled by type IIb myofibers, which express the fastest myosin IIb in limb muscles, encoded by MYH4. In contrast, larger mammals, including humans, exhibit a marked reduction or complete absence of type IIb myofibers and MYH4 expression, favoring slower-contracting myofiber types. The evolutionary shift away from MYH4 expression in larger mammals and the underlying regulatory mechanisms remain poorly understood. Previously, we identified the large Maf transcription factor family (Mafa, Mafb, Maf) as principal regulators of type IIb myofiber determination in mice. Here, we provide the first evidence that the large MAFs specifically induces MYH4 expression in the skeletal muscles of large mammals, including humans and bovine. Furthermore, induction of MYH4 by large MAFs significantly enhances the glycolytic capacity of human myotubes, as evidenced by flux analyzer data and RNA-seq showing the upregulation of numerous genes associated with glucose metabolism. Lastly, RNA-seq analysis of human muscle biopsies reveals a positive correlation between MAFA, MAF, and MYH4 expression. Our findings propose that the large MAFs promotes the formation of the fastest type IIb myofibers in the skeletal muscles of large mammals. This discovery not only elucidates the mechanisms underlying the loss of type IIb myofibers in larger mammals but also holds potential implications for enhancing athletic performance and counteracting the loss of fast-twitch myofibers associated with aging.
2025-07-30 | GSE283853 | GEO
Project description:Skeletal muscle myofibers, categorized into slow-twitch (type I) and fast-twitch (type II) fibers based on myosin heavy chain (MHC) isoforms, exhibit varying fatigue resistance and metabolic reliance. Type I myofibers are fatigue-resistant with high mitochondrial density and oxidative metabolism, while Type II myofibers fatigue quickly due to glycolytic metabolism and fewer mitochondria. Endurance training induces remodeling of myofiber and mitochondrial, increasing slow-twitch myofibers and enhancing mitochondrial oxidative capacity, improving muscle fitness. In our study, conducted using single-cell techniques, we delved deeply into the transcriptomic differences between type I and type IIb myofibers. In response to endurance training, type I myofibers exhibited heightened signals in essential adaptive responses, such as fatty acid oxidation, mitochondrial biogenesis, and protein synthesis, compared to type IIb myofibers. By analyzing untrained myofibers, we identified specific signaling pathways that explain the differences in their responses to endurance training. These findings provide nuanced insights into the molecular mechanisms governing endurance adaptations in fast and slow-twitch muscles, offering valuable guidance for tailored exercise routines and potential therapeutic interventions.
2024-12-31 | GSE244547 | GEO
Project description:The large Maf transcription factor family (Mafa, Mafb, Maf) induced MyHCIIB in human myotubes.
2025-11-27 | PXD058314 | JPOST Repository
Project description:Skeletal muscle denervation is a characteristic feature of neuromuscular diseases such as amyotrophic lateral sclerosis (ALS) and sarcopenia, leading to atrophy, loss of muscle strength, and poor patient outcomes. Myofibers are typically classified into slow oxidative and fast glycolytic types based on their contractile and metabolic properties. Neuromuscular diseases predominantly affect fast myofibers, while slow myofibers are relatively spared. However, the mechanisms underlying the heightened susceptibility of fast myofibers to disease and atrophy remain unclear. To investigate this, we analyzed the transcriptional profiles of innervated and denervated myonuclei. Our findings revealed that the fast muscle gene program and the transcription factor Maf are repressed during denervation. Notably, overexpression of Maf in the skeletal muscles of mice prevented loss of muscle mass and myofiber atrophy caused by denervation. Single-nucleus RNA sequencing and ATAC sequencing demonstrated that Maf overexpression reprogrammed denervated myonuclei by repressing atrophic gene programs and reactivating fast muscle gene expression. Similar repression of fast muscle genes and Maf was observed in muscles from mice and humans with ALS. Consistent with these findings, Maf overexpression in human skeletal muscle cells induced the expression of fast muscle genes while suppressing atrophic gene expression. Our findings highlight a key role for Maf in maintaining muscle mass and demonstrate that its repression contributes to the progression of neuromuscular diseases in both mice and humans. Modulating Maf activity could offer a promising therapeutic strategy to preserve skeletal muscle function during disease, aging, or injury.
2025-05-29 | GSE298184 | GEO
Project description:Skeletal muscle denervation is a characteristic feature of neuromuscular diseases such as amyotrophic lateral sclerosis (ALS) and sarcopenia, leading to atrophy, loss of muscle strength, and poor patient outcomes. Myofibers are typically classified into slow oxidative and fast glycolytic types based on their contractile and metabolic properties. Neuromuscular diseases predominantly affect fast myofibers, while slow myofibers are relatively spared. However, the mechanisms underlying the heightened susceptibility of fast myofibers to disease and atrophy remain unclear. To investigate this, we analyzed the transcriptional profiles of innervated and denervated myonuclei. Our findings revealed that the fast muscle gene program and the transcription factor Maf are repressed during denervation. Notably, overexpression of Maf in the skeletal muscles of mice prevented loss of muscle mass and myofiber atrophy caused by denervation. Single-nucleus RNA sequencing and ATAC sequencing demonstrated that Maf overexpression reprogrammed denervated myonuclei by repressing atrophic gene programs and reactivating fast muscle gene expression. Similar repression of fast muscle genes and Maf was observed in muscles from mice and humans with ALS. Consistent with these findings, Maf overexpression in human skeletal muscle cells induced the expression of fast muscle genes while suppressing atrophic gene expression. Our findings highlight a key role for Maf in maintaining muscle mass and demonstrate that its repression contributes to the progression of neuromuscular diseases in both mice and humans. Modulating Maf activity could offer a promising therapeutic strategy to preserve skeletal muscle function during disease, aging, or injury.
2025-05-29 | GSE298187 | GEO
Project description:Background: skeletal muscle is a complex, versatile tissue composed of a variety of functionally diverse fiber types. Although the biochemical, structural and functional properties of myofibers have been the subject of intense investigation for the last decades, understanding molecular processes regulating fiber type diversity is still complicated by the heterogeneity of cell types present in the whole muscle organ. Methodology/Principal Findings: we have produced a first catalogue of genes expressed in mouse slow-oxidative (type 1) and fast-glycolytic (type 2B) fibers through transcriptome analysis at the single fiber level (microgenomics). Individual fibers were obtained from murine soleus and EDL muscles and initially classified by myosin heavy chain isoform content. Gene expression profiling on high density DNA oligonucleotide microarrays showed that both qualitative and quantitative improvements were achieved, compared to results with standard muscle homogenate. First, myofiber profiles were virtually free from non-muscle transcriptional activity. Second, thousands of muscle-specific genes were identified, leading to a better definition of gene signatures in the two fiber types as well as the detection of metabolic and signaling pathways that are differentially activated in specific fiber types. Several regulatory proteins showed preferential expression in slow myofibers. Discriminant analysis revealed novel genes that could be useful for fiber type functional classification. Conclusions/Significance: as gene expression analyses at the single fiber level significantly increased the resolution power, this innovative approach would allow a better understanding of the adaptive transcriptomic transitions occurring in myofibers under physiological and pathological conditions.
2011-07-21 | GSE23244 | GEO
Project description:Effect of endurance training on expression signatures of mouse type I and type IIb myofibers
| PRJNA1023534 | ENA
Project description:Background: skeletal muscle is a complex, versatile tissue composed of a variety of functionally diverse fiber types. Although the biochemical, structural and functional properties of myofibers have been the subject of intense investigation for the last decades, understanding molecular processes regulating fiber type diversity is still complicated by the heterogeneity of cell types present in the whole muscle organ. Methodology/Principal Findings: we have produced a first catalogue of genes expressed in mouse slow-oxidative (type 1) and fast-glycolytic (type 2B) fibers through transcriptome analysis at the single fiber level (microgenomics). Individual fibers were obtained from murine soleus and EDL muscles and initially classified by myosin heavy chain isoform content. Gene expression profiling on high density DNA oligonucleotide microarrays showed that both qualitative and quantitative improvements were achieved, compared to results with standard muscle homogenate. First, myofiber profiles were virtually free from non-muscle transcriptional activity. Second, thousands of muscle-specific genes were identified, leading to a better definition of gene signatures in the two fiber types as well as the detection of metabolic and signaling pathways that are differentially activated in specific fiber types. Several regulatory proteins showed preferential expression in slow myofibers. Discriminant analysis revealed novel genes that could be useful for fiber type functional classification. Conclusions/Significance: as gene expression analyses at the single fiber level significantly increased the resolution power, this innovative approach would allow a better understanding of the adaptive transcriptomic transitions occurring in myofibers under physiological and pathological conditions. EDL and soleus muscles were incubated with type I collagenase to dissociate intact myofibres that were separated under stereo microscope from the bulk of hyper contracted fibres. Isolated myofibres were divided in two parts: one was immersed in Laemmli buffer for fibre typing; the other was placed in RNA extraction buffer for RNA amplification. We analyzed the transcription profiles of 10 biological replicas of type 2B single muscle fibres from EDL and 10 biological replicas of type 1 single muscle fibres from soleus. Microarray competitive hybridizations were carried out against an artificial control with a balanced composition of type 1 and type 2B fibres (20 hybridizations). Each oligonucleotide is spotted in two replicates on the glass slide, so for every data two intra-slide replicas are present. The control was created as follows: three couples of soleus and EDL muscles were removed from 3 different mice and treated with collagenase. Total RNA was extracted separately from EDL and soleus muscles. By mixing about 1/3 RNA from EDL and 2/3 RNA from soleus muscles the control had approximately the same contributions of type 1 and type 2B fibres. Purified RNA samples from single fibres and from control were amplified twice using the Amino Allyl MessageAmpM-bM-^DM-" II aRNA Amplification Kit (Ambion).
2011-07-20 | E-GEOD-23244 | biostudies-arrayexpress
Project description:Dystrophic single myofibers vs. control single myofibers
| PRJNA125993 | ENA
Project description:Dystrophic single myofibers vs control single myofibers
| PRJNA126531 | ENA