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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 -
Current Topics in Developmental Biology 2018Rhabdomyosarcoma is a mesenchymal malignancy associated with the skeletal muscle lineage and is also the most common pediatric soft tissue cancer. Between the two... (Review)
Review
Rhabdomyosarcoma is a mesenchymal malignancy associated with the skeletal muscle lineage and is also the most common pediatric soft tissue cancer. Between the two pediatric subtypes, embryonal and alveolar rhabdomyosarcoma, the alveolar subtype is generally more aggressive and high-risk. Despite intensive multimodal therapy, patients with high-risk rhabdomyosarcoma continue to have poor prognosis. In this chapter we address the mechanisms underlying the dysregulation of myogenesis in rhabdomyosarcoma. We specifically focus on recently identified signaling pathways that function to inhibit myogenesis and how similar functions have been shown to overlap in rhabdomyosarcoma, potentially contributing to the disease.
Topics: Cell Differentiation; Gene Expression Regulation, Developmental; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Models, Genetic; Muscle Development; Muscle, Skeletal; Rhabdomyosarcoma; Signal Transduction
PubMed: 29305002
DOI: 10.1016/bs.ctdb.2017.10.007 -
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 -
Experimental Cell Research Oct 2022Skeletal muscle development and regeneration is governed by the combined action of Myf5, MyoD, Mrf4 and MyoG, also known as the myogenic regulatory factors (MRFs). These... (Review)
Review
Skeletal muscle development and regeneration is governed by the combined action of Myf5, MyoD, Mrf4 and MyoG, also known as the myogenic regulatory factors (MRFs). These transcription factors are expressed in a highly spatio-temporal restricted manner, ensuring the significant functional and metabolic diversity observed between the different muscle groups. In this review, we will discuss the multiple layers of regulation that contribute to the control of the exquisite expression patterns of the MRFs in particular, and of myogenic genes in general. We will highlight all major regulatory processes that play a role in myogenesis: from those that modulate chromatin status and transcription competence, such as DNA methylation, histone modification, chromatin remodeling, or non-coding RNAs, to those that control transcript and protein processing and modification, such as alternative splicing, polyadenylation, other mRNA modifications, or post-translational protein modifications. All these processes are exquisitely and tightly coordinated to ensure the proper activation, maintenance and termination of the myogenic process.
Topics: Chromatin Assembly and Disassembly; Gene Expression; Gene Expression Regulation; Muscle Development; Muscle, Skeletal; Myogenic Regulatory Factors; Transcription Factors
PubMed: 35926660
DOI: 10.1016/j.yexcr.2022.113299 -
International Journal of Molecular... Sep 2021Primary cilia are non-motile, cell cycle-associated organelles that can be found on most vertebrate cell types. Comprised of microtubule bundles organised into an... (Review)
Review
Primary cilia are non-motile, cell cycle-associated organelles that can be found on most vertebrate cell types. Comprised of microtubule bundles organised into an axoneme and anchored by a mature centriole or basal body, primary cilia are dynamic signalling platforms that are intimately involved in cellular responses to their extracellular milieu. Defects in ciliogenesis or dysfunction in cilia signalling underlie a host of developmental disorders collectively referred to as ciliopathies, reinforcing important roles for cilia in human health. Whilst primary cilia have long been recognised to be present in striated muscle, their role in muscle is not well understood. However, recent studies indicate important contributions, particularly in skeletal muscle, that have to date remained underappreciated. Here, we explore recent revelations that the sensory and signalling functions of cilia on muscle progenitors regulate cell cycle progression, trigger differentiation and maintain a commitment to myogenesis. Cilia disassembly is initiated during myoblast fusion. However, the remnants of primary cilia persist in multi-nucleated myotubes, and we discuss their potential role in late-stage differentiation and myofiber formation. Reciprocal interactions between cilia and the extracellular matrix (ECM) microenvironment described for other tissues may also inform on parallel interactions in skeletal muscle. We also discuss emerging evidence that cilia on fibroblasts/fibro-adipogenic progenitors and myofibroblasts may influence cell fate in both a cell autonomous and non-autonomous manner with critical consequences for skeletal muscle ageing and repair in response to injury and disease. This review addresses the enigmatic but emerging role of primary cilia in satellite cells in myoblasts and myofibers during myogenesis, as well as the wider tissue microenvironment required for skeletal muscle formation and homeostasis.
Topics: Animals; Axoneme; Cell Cycle; Cell Differentiation; Centrosome; Cilia; Cytoskeleton; Extracellular Matrix; Humans; Muscle Development; Muscle Fibers, Skeletal; Muscle, Skeletal; Myoblasts; Organelles; Signal Transduction
PubMed: 34502512
DOI: 10.3390/ijms22179605 -
Cells Aug 2019Circular RNA (circRNA) is a novel class of non-coding RNA generated by pre-mRNA back splicing, which is characterized by a closed-loop structure. Although circRNAs were... (Review)
Review
Circular RNA (circRNA) is a novel class of non-coding RNA generated by pre-mRNA back splicing, which is characterized by a closed-loop structure. Although circRNAs were firstly reported decades ago, their regulatory roles have not been discovered until recently. In this review, we discussed the putative biogenesis pathways and regulatory functions of circRNAs. Recent studies showed that circRNAs are abundant in skeletal muscle tissue, and their expression levels are regulated during muscle development and aging. We, thus, characterized the expression profile of circRNAs in skeletal muscle and discussed regulatory functions and mechanism-of-action of specific circRNAs in myogenesis. The future investigation into the roles of circRNAs in both physiological and pathological conditions may provide novel insights in skeletal muscle development and provide new therapeutic strategies for muscular diseases.
Topics: Animals; Gene Expression Regulation, Developmental; Humans; Muscle Development; Muscle, Skeletal; RNA, Circular
PubMed: 31412632
DOI: 10.3390/cells8080885 -
International Journal of Molecular... Jun 2023As an organ system, skeletal muscle is essential for the generation of energy that underpins muscle contraction, plays a critical role in controlling energy balance and... (Review)
Review
As an organ system, skeletal muscle is essential for the generation of energy that underpins muscle contraction, plays a critical role in controlling energy balance and insulin-dependent glucose homeostasis, as well as vascular well-being, and regenerates following injury. To achieve homeostasis, there is requirement for "cross-talk" between the myogenic and vascular components and their regulatory factors that comprise skeletal muscle. Accordingly, this review will describe the following: [a] the embryonic cell-signaling events important in establishing vascular and myogenic cell-lineage, the cross-talk between endothelial cells (EC) and myogenic precursors underpinning the development of muscle, its vasculature and the satellite-stem-cell (SC) pool, and the EC-SC cross-talk that maintains SC quiescence and localizes ECs to SCs and angio-myogenesis postnatally; [b] the vascular-myocyte cross-talk and the actions of insulin on vasodilation and capillary surface area important for the uptake of glucose/insulin by myofibers and vascular homeostasis, the microvascular-myocyte dysfunction that characterizes the development of insulin resistance, diabetes and hypertension, and the actions of estrogen on muscle vasodilation and growth in adults; [c] the role of estrogen in utero on the development of fetal skeletal-muscle microvascularization and myofiber hypertrophy required for metabolic/vascular homeostasis after birth; [d] the EC-SC interactions that underpin myofiber vascular regeneration post-injury; and [e] the role of the skeletal-muscle vasculature in Duchenne muscular dystrophy.
Topics: Endothelial Cells; Muscle, Skeletal; Muscle Contraction; Insulin; Glucose; Muscle Development
PubMed: 37445602
DOI: 10.3390/ijms241310425 -
Journal of Cellular Physiology Jan 2020Skeletal muscle development is a highly organized process controlled by evolutionarily conserved networks of transcription factors, transferrable signaling molecules,... (Review)
Review
Skeletal muscle development is a highly organized process controlled by evolutionarily conserved networks of transcription factors, transferrable signaling molecules, and noncoding RNAs that coordinate the expression of large numbers of genes. MicroRNAs (miRNAs) have emerged as prominent players of multiple biological processes by silence of specific mRNAs or by suppression of protein translation. It has become to be clear cumulatively that miRNAs control of expression of gene targets are particularly important during skeletal myogenesis. Signaling pathways, especially IGF/AKT/mTOR pathway and TGF-β signaling, have also determined to act as critical regulators in the regulation of myogenic program. In the last decades, growing evidence has seen a rapid expansion of our knowledge of miRNA-mediated control of expression of target genes and signaling pathways, in which miRNAs coordinately regulate myogenic process through their targets or through signaling pathways. Here, we summarize the current findings of miRNAs and signaling pathways in the regulation of skeletal myogenesis, focusing on miRNAs' target genes and IGF/AKT/mTOR pathway and TGF-β signaling.
Topics: Animals; Gene Expression Regulation, Developmental; Humans; MicroRNAs; Muscle Development; Muscle, Skeletal
PubMed: 31230374
DOI: 10.1002/jcp.28986 -
Cells Oct 2023Maintenance of skeletal muscle quantity and quality is essential to ensure various vital functions of the body. Muscle homeostasis is regulated by multiple cytoskeletal... (Review)
Review
Maintenance of skeletal muscle quantity and quality is essential to ensure various vital functions of the body. Muscle homeostasis is regulated by multiple cytoskeletal proteins and myogenic transcriptional programs responding to endogenous and exogenous signals influencing cell structure and function. Since actin is an essential component in cytoskeleton dynamics, actin-binding proteins (ABPs) have been recognized as crucial players in skeletal muscle health and diseases. Hence, dysregulation of ABPs leads to muscle atrophy characterized by loss of mass, strength, quality, and capacity for regeneration. This comprehensive review summarizes the recent studies that have unveiled the role of ABPs in actin cytoskeletal dynamics, with a particular focus on skeletal myogenesis and diseases. This provides insight into the molecular mechanisms that regulate skeletal myogenesis via ABPs as well as research avenues to identify potential therapeutic targets. Moreover, this review explores the implications of non-coding RNAs (ncRNAs) targeting ABPs in skeletal myogenesis and disorders based on recent achievements in ncRNA research. The studies presented here will enhance our understanding of the functional significance of ABPs and mechanotransduction-derived myogenic regulatory mechanisms. Furthermore, revealing how ncRNAs regulate ABPs will allow diverse therapeutic approaches for skeletal muscle disorders to be developed.
Topics: Microfilament Proteins; Actins; Mechanotransduction, Cellular; Muscle, Skeletal; RNA, Untranslated; Muscle Development
PubMed: 37947600
DOI: 10.3390/cells12212523 -
Acta Histochemica 2015Myogenesis is controlled by an elaborate system of extrinsic and intrinsic regulatory mechanisms in all development stages. The aim of this review is to provide an... (Review)
Review
Myogenesis is controlled by an elaborate system of extrinsic and intrinsic regulatory mechanisms in all development stages. The aim of this review is to provide an overview of the different stages of myogenesis and muscle differentiation in mammals, starting from somitogenesis and analysis of the different portions that constitute the mature somite. Particular attention was paid to regulatory genes, in addition to mesodermal stem cells, which represent the earliest elements of myogenesis. Finally, the crucial role of growth factors, molecules of vital importance in contractile regulation, hormones and their function in skeletal muscle differentiation, growth and metabolism, and the role played by central nervous system, are discussed.
Topics: Animals; Cell Differentiation; Gene Expression Regulation, Developmental; Humans; Intercellular Signaling Peptides and Proteins; Muscle Development; Muscle, Skeletal; Somites; Stem Cells
PubMed: 25850375
DOI: 10.1016/j.acthis.2015.02.011