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Journal of Functional Morphology and... Dec 2023Regimented resistance training (RT) has been shown to promote increases in muscle size. When engaging in RT, practitioners often emphasize the importance of appropriate... (Review)
Review
Regimented resistance training (RT) has been shown to promote increases in muscle size. When engaging in RT, practitioners often emphasize the importance of appropriate exercise technique, especially when trying to maximize training adaptations (e.g., hypertrophy). This narrative review aims to synthesize existing evidence on what constitutes proper RT exercise technique for maximizing muscle hypertrophy, focusing on variables such as exercise-specific kinematics, contraction type, repetition tempo, and range of motion (ROM). We recommend that when trying to maximize hypertrophy, one should employ a ROM that emphasizes training at long muscle lengths while also employing a repetition tempo between 2 and 8 s. More research is needed to determine whether manipulating the duration of either the eccentric or concentric phase further enhances hypertrophy. Guidelines for body positioning and movement patterns are generally based on implied theory from applied anatomy and biomechanics. However, existing research on the impact of manipulating these aspects of exercise technique and their effect on hypertrophy is limited; it is therefore suggested that universal exercise-specific kinematic guidelines are followed and adopted in accordance with the above recommendations. Future research should investigate the impact of stricter versus more lenient exercise technique variations on hypertrophy.
PubMed: 38249086
DOI: 10.3390/jfmk9010009 -
Journal of Cachexia, Sarcopenia and... Dec 2023Lactate, a glycolytic metabolite mainly produced in muscles, has been suggested to regulate myoblast differentiation, although the underlying mechanism remains elusive....
BACKGROUND
Lactate, a glycolytic metabolite mainly produced in muscles, has been suggested to regulate myoblast differentiation, although the underlying mechanism remains elusive. Recently, lactate-mediated histone lactylation is identified as a novel epigenetic modification that promotes gene transcription.
METHODS
We used mouse C2C12 cell line and 2-month-old male mice as in vitro and in vivo models, respectively. These models were treated with lactate to explore the biological function and latent mechanism of lactate-derived histone lactylation on myogenic differentiation by quantitative real-time PCR, western blotting, immunofluorescence staining, chromatin immunoprecipitation, cleavage under targets and tagmentation assay and RNA sequencing.
RESULTS
Using immunofluorescence staining and western blotting, we proposed that lactylation might occur in the histones. Inhibition of lactate production or intake both impaired myoblast differentiation, accompanied by diminished lactylation in the histones. Using lactylation site-specific antibodies, we demonstrated that lactate preferentially increased H3K9 lactylation (H3K9la) during myoblast differentiation (CT VS 5, 10, 15, 20, 25 mM lactate treatment, P = 0.0012, P = 0.0007, and the rest of all P < 0.0001). Notably, inhibiting H3K9la using P300 antagonist could block lactate-induced myogenesis. Through combined omics analysis using cleavage under targets and tagmentation assay and RNA sequencing, we further identified Neu2 as a potential target gene of H3K9la. IGV software analysis (P = 0.0013) and chromatin immunoprecipitation-qPCR assay (H3K9la %Input, LA group = 9.0076, control group = 2.7184, IgG = 0.3209) confirmed that H3K9la is enriched in the promoter region of Neu2. Moreover, siRNAs or inhibitors against Neu2 both abrogated myoblast differentiation despite lactate treatment, suggesting that Neu2 is required for lactate-mediated myoblast differentiation.
CONCLUSIONS
Our findings provide novel understanding of histone lysine lactylation, suggesting its role in myogenesis, and as potential therapeutic targets for muscle diseases.
Topics: Animals; Male; Mice; Cell Line; Histones; Lactic Acid; Muscle Development; Up-Regulation
PubMed: 37919243
DOI: 10.1002/jcsm.13363 -
Nature Communications Jul 2023Skeletal muscle fibers express distinct gene programs during development and maturation, but the underlying gene regulatory networks that confer stage-specific myofiber...
Skeletal muscle fibers express distinct gene programs during development and maturation, but the underlying gene regulatory networks that confer stage-specific myofiber properties remain unknown. To decipher these distinctive gene programs and how they respond to neural activity, we generated a combined multi-omic single-nucleus RNA-seq and ATAC-seq atlas of mouse skeletal muscle development at multiple stages of embryonic, fetal, and postnatal life. We found that Myogenin, Klf5, and Tead4 form a transcriptional complex that synergistically activates the expression of muscle genes in developing myofibers. During myofiber maturation, the transcription factor Maf acts as a transcriptional switch to activate the mature fast muscle gene program. In skeletal muscles of mutant mice lacking voltage-gated L-type Ca channels (Cav1.1), Maf expression and myofiber maturation are impaired. These findings provide a transcriptional atlas of muscle development and reveal genetic links between myofiber formation, maturation, and contraction.
Topics: Mice; Animals; Muscle Fibers, Skeletal; Muscle, Skeletal; Gene Expression Regulation; Transcription Factors; Cell Differentiation
PubMed: 37468485
DOI: 10.1038/s41467-023-40073-8 -
Cell Proliferation Sep 2023Skeletal muscle is a complex heterogeneous tissue and characterizing its cellular heterogeneity and transcriptional and epigenetic signatures are important for...
Skeletal muscle is a complex heterogeneous tissue and characterizing its cellular heterogeneity and transcriptional and epigenetic signatures are important for understanding the details of its ontogeny. In our study, we applied scRNA-seq and scATAC-seq to investigate the cell types, molecular features, transcriptional and epigenetic regulation, and patterns of developing bovine skeletal muscle from gestational, lactational and adult stages. Detailed molecular analyses were used to dissect cellular heterogeneity, and we deduced the differentiation trajectory of myogenic cells and uncovered their dynamic gene expression profiles. SCENIC analysis was performed to demonstrate key regulons during cell fate decisions. We explored the future expression states of these heterogeneous cells by RNA velocity analysis and found extensive networks of intercellular communication using the toolkit CellChat. Moreover, the transcriptomic and chromatin accessibility modalities were confirmed to be highly concordant, and integrative analysis of chromatin accessibility and gene expression revealed key transcriptional regulators acting during myogenesis. In bovine skeletal muscle, by scRNA-seq and scATAC-seq analysis, different cell types such as adipocytes, endothelial cells, fibroblasts, lymphocytes, monocytes, pericyte cells and eight skeletal myogenic subpopulations were identified at the three developmental stages. The pseudotime trajectory exhibited a distinct sequential ordering for these myogenic subpopulations and eight distinct gene clusters were observed according to their expression pattern. Moreover, specifically expressed TFs (such as MSC, MYF5, MYOD1, FOXP3, ESRRA, BACH1, SIX2 and ATF4) associated with muscle development were predicted, and likely future transcriptional states of individual cells and the developmental dynamics of differentiation among neighbouring cells were predicted. CellChat analysis on the scRNA-seq data set then classified many ligand-receptor pairs among these cell clusters, which were further categorized into significant signalling pathways, including BMP, IGF, WNT, MSTN, ANGPTL, TGFB, TNF, VEGF and FGF. Finally, scRNA-seq and scATAC-seq results were successfully integrated to reveal a series of specifically expressed TFs that are likely to be candidates for the promotion of cell fate transition during bovine skeletal muscle development. Overall, our results outline a single-cell dynamic chromatin/transcriptional landscape for normal bovine skeletal muscle development; these provide an important resource for understanding the structure and function of mammalian skeletal muscle, which will promote research into its biology.
Topics: Cattle; Animals; Chromatin; Epigenesis, Genetic; Endothelial Cells; Transcription Factors; Muscle Development; Mammals
PubMed: 36855961
DOI: 10.1111/cpr.13430 -
Advanced Science (Weinheim,... Dec 2023Skeletal muscle comprises a large, heterogeneous assortment of cell populations that interact to maintain muscle homeostasis, but little is known about the mechanism...
Skeletal muscle comprises a large, heterogeneous assortment of cell populations that interact to maintain muscle homeostasis, but little is known about the mechanism that controls myogenic development in response to artificial selection. Different pig (Sus scrofa) breeds exhibit distinct muscle phenotypes resulting from domestication and selective breeding. Using unbiased single-cell transcriptomic sequencing analysis (scRNA-seq), the impact of artificial selection on cell profiles is investigated in neonatal skeletal muscle of pigs. This work provides panoramic muscle-resident cell profiles and identifies novel and breed-specific cells, mapping them on pseudotime trajectories. Artificial selection has elicited significant changes in muscle-resident cell profiles, while conserving signs of generational environmental challenges. These results suggest that fibro-adipogenic progenitors serve as a cellular interaction hub and that specific transcription factors identified here may serve as candidate target regulons for the pursuit of a specific muscle phenotype. Furthermore, a cross-species comparison of humans, mice, and pigs illustrates the conservation and divergence of mammalian muscle ontology. The findings of this study reveal shifts in cellular heterogeneity, novel cell subpopulations, and their interactions that may greatly facilitate the understanding of the mechanism underlying divergent muscle phenotypes arising from artificial selection.
Topics: Humans; Animals; Mice; Muscle, Skeletal; Phenotype; Adipogenesis; Muscle Development; RNA; Mammals
PubMed: 37870215
DOI: 10.1002/advs.202305080 -
Nature Communications Nov 2023MyoD is a skeletal muscle-specifically expressed transcription factor and plays a critical role in regulating myogenesis during muscle development and regeneration....
MyoD is a skeletal muscle-specifically expressed transcription factor and plays a critical role in regulating myogenesis during muscle development and regeneration. However, whether myofibers-expressed MyoD exerts its metabolic function in regulating whole body energy homeostasis in vivo remains largely unknown. Here, we report that genetic deletion of Myod in male mice enhances the oxidative metabolism of muscle and, intriguingly, renders the male mice resistant to high fat diet-induced obesity. By performing lipidomic analysis in muscle-conditioned medium and serum, we identify 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC) as a muscle-released lipid that is responsible for MyoD-orchestrated body energy homeostasis in male Myod KO mice. Functionally, the administration of DLPC significantly ameliorates HFD-induced obesity in male mice. Mechanistically, DLPC is found to induce white adipose browning via lipid peroxidation-mediated p38 signaling in male mice. Collectively, our findings not only uncover a novel function of MyoD in controlling systemic energy homeostasis through the muscle-derived lipokine DLPC but also suggest that the DLPC might have clinical potential for treating obesity in humans.
Topics: Humans; Male; Animals; Mice; Obesity; Muscle, Skeletal; Transcription Factors; Gene Expression Regulation; Homeostasis; Diet, High-Fat; Energy Metabolism; Mice, Inbred C57BL; Adipose Tissue, White; Adipose Tissue, Brown
PubMed: 38036537
DOI: 10.1038/s41467-023-43402-z -
Differentiation; Research in Biological... 2024Fibroblast Growth Factor 6 (FGF6), also referred to as HST2 or HBGF6, is a member of the Fibroblast Growth Factor (FGF), the Heparin Binding Growth Factor (HBGF) and the... (Review)
Review
Fibroblast Growth Factor 6 (FGF6), also referred to as HST2 or HBGF6, is a member of the Fibroblast Growth Factor (FGF), the Heparin Binding Growth Factor (HBGF) and the Heparin Binding Secretory Transforming Gene (HST) families. The genomic and protein structure of FGF6 is highly conserved among varied species, as is its expression in muscle and muscle progenitor cells. Like other members of the FGF family, FGF6 regulates cell proliferation, differentiation, and migration. Specifically, it plays key roles in myogenesis and muscular regeneration, angiogenesis, along with iron transport and lipid metabolism. Similar to others from the FGF family, FGF6 also possesses oncogenic transforming activity, and as such is implicated in a variety of cancers.
Topics: Humans; Animals; Cell Differentiation; Fibroblast Growth Factor 6; Muscle Development; Cell Proliferation; Neoplasms; Cell Movement
PubMed: 38626632
DOI: 10.1016/j.diff.2024.100780 -
The Journal of International Medical... Aug 2023Sclerostin, a protein encoded by the sclerostin () gene, is mostly expressed in osteocytes. First described in the pathogenesis of three disorders, sclerosteosis, van... (Review)
Review
Sclerostin, a protein encoded by the sclerostin () gene, is mostly expressed in osteocytes. First described in the pathogenesis of three disorders, sclerosteosis, van Buchem's disease, and craniodiaphyseal dysplasia, sclerostin has been identified as an important regulator of bone homeostasis, controlling bone formation by osteoblasts through inhibition of the canonical Wnt signaling pathway. Recent studies have highlighted a hypothetical role of sclerostin in myogenesis, thus modulating the interaction between bone and muscle. This narrative review provides an overview of the clinical implications of sclerostin modulation on skeletal muscle mass and function, and bone metabolism. Improving knowledge about muscle-bone crosstalk may represent a turning point in the development of therapeutic strategies for musculoskeletal disorders, particularly osteosarcopenia.
Topics: Humans; Hyperostosis; Knowledge; Muscles; Osteoblasts; Osteogenesis
PubMed: 37632438
DOI: 10.1177/03000605231193293 -
Journal of Advanced Research Jan 2024Investigating the genetic markers and genomic signatures related to chicken meat production by combing multi-omics methods could provide new insights into modern chicken...
INTRODUCTION
Investigating the genetic markers and genomic signatures related to chicken meat production by combing multi-omics methods could provide new insights into modern chicken breeding technology systems.
OBJECT
Chicken is one of the most efficient and environmentally friendly livestock, especially the fast-growing white-feathered chicken (broiler), which is well known for high meat yield, but the underlying genetic basis is poorly understood.
METHOD
We generated whole-genome resequencing of three purebred broilers (n = 748) and six local breeds/lines (n = 114), and sequencing data of twelve chicken breeds (n = 199) were obtained from the NCBI database. Additionally, transcriptome sequencing of six tissues from two chicken breeds (n = 129) at two developmental stages was performed. A genome-wide association study combined with cis-eQTL mapping and the Mendelian randomization was applied.
RESULT
We identified > 17 million high-quality SNPs, of which 21.74% were newly identified, based on 21 chicken breeds/lines. A total of 163 protein-coding genes underwent positive selection in purebred broilers, and 83 genes were differentially expressed between purebred broilers and local chickens. Notably, muscle development was proven to be the major difference between purebred broilers and local chickens, or ancestors, based on genomic and transcriptomic evidence from multiple tissues and stages. The MYH1 gene family showed the top selection signatures and muscle-specific expression in purebred broilers. Furthermore, we found that the causal gene SOX6 influenced breast muscle yield and also related to myopathy occurrences. A refined haplotype was provided, which had a significant effect on SOX6 expression and phenotypic changes.
CONCLUSION
Our study provides a comprehensive atlas comprising the typical genomic variants and transcriptional characteristics for muscle development and suggests a new regulatory target (SOX6-MYH1s axis) for breast muscle yield and myopathy, which could aid in the development of genome-scale selective breeding aimed at high meat yield in broiler chickens.
Topics: Animals; Chickens; Genome-Wide Association Study; Genomics; Gene Expression Profiling; Meat; Muscular Diseases
PubMed: 36871617
DOI: 10.1016/j.jare.2023.02.016 -
Development (Cambridge, England) May 2024Proper embryonic development depends on the timely progression of a genetic program. One of the key mechanisms for achieving precise control of developmental timing is... (Review)
Review
Proper embryonic development depends on the timely progression of a genetic program. One of the key mechanisms for achieving precise control of developmental timing is to use gene expression oscillations. In this Review, we examine how gene expression oscillations encode temporal information during vertebrate embryonic development by discussing the gene expression oscillations occurring during somitogenesis, neurogenesis, myogenesis and pancreas development. These oscillations play important but varied physiological functions in different contexts. Oscillations control the period of somite formation during somitogenesis, whereas they regulate the proliferation-to-differentiation switch of stem cells and progenitor cells during neurogenesis, myogenesis and pancreas development. We describe the similarities and differences of the expression pattern in space (i.e. whether oscillations are synchronous or asynchronous across neighboring cells) and in time (i.e. different time scales) of mammalian Hes/zebrafish Her genes and their targets in different tissues. We further summarize experimental evidence for the functional role of their oscillations. Finally, we discuss the outstanding questions for future research.
Topics: Animals; Embryonic Development; Gene Expression Regulation, Developmental; Humans; Somites; Muscle Development; Neurogenesis; Pancreas; Cell Differentiation
PubMed: 38727565
DOI: 10.1242/dev.202191