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Organogenesis 2010During embryogenesis a timely and coordinated expression of different subsets of genes drives the formation of skeletal muscles in response to developmental cues. In... (Review)
Review
During embryogenesis a timely and coordinated expression of different subsets of genes drives the formation of skeletal muscles in response to developmental cues. In this review, we will summarize the most recent advances on the "epigenetic network" that promotes the transcription of selective groups of genes in muscle progenitors, through the concerted action of chromatin-associated complexes that modify histone tails and microRNAs (miRNAs). These epigenetic players cooperate to establish focal domains of euchromatin, which facilitates gene transcription, and large portions of heterochromatin, which precludes inappropriate gene expression. We also discuss the analogies and differences in the transcriptional and the epigenetic networks driving developmental and adult myogenesis. The elucidation of the epigenetic basis controlling skeletal myogenesis during development and adult life will facilitate experimental strategies toward generating muscle stem cells, either by reprogramming embryonic stem cells or by inducing pluripotency in adult skeletal muscles. During embryogenesis a timely and coordinated expression of different subsets of genes drives the formation of skeletal muscles in response to developmental cues. In this review, we will summarize the most recent advances on the "epigenetic network" that promotes the transcription of selective groups of genes in muscle progenitors, through the concerted action of chromatin-associated complexes that modify histone tails and microRNAs (miRNAs). These epigenetic players cooperate to establish focal domains of euchromatin, which facilitates gene transcription, and large portions of heterochromatin, which precludes inappropriate gene expression. We also discuss the analogies and differences in the transcriptional and the epigenetic networks driving developmental and adult myogenesis. The elucidation of the epigenetic basis controlling skeletal myogenesis during development and adult life will facilitate experimental strategies toward generating muscle stem cells, either by reprogramming embryonic stem cells or by inducing pluripotency in adult skeletal muscles.
Topics: Animals; Cell Differentiation; Embryonic Stem Cells; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Humans; MicroRNAs; Muscle Development; Muscle, Skeletal
PubMed: 20592865
DOI: 10.4161/org.6.1.11293 -
Cells Dec 2022Glycosylation is an important mechanism regulating various biological processes, including intercellular signaling and adhesion. α-1,6-fucosyltransferase (Fut8) belongs...
Glycosylation is an important mechanism regulating various biological processes, including intercellular signaling and adhesion. α-1,6-fucosyltransferase (Fut8) belongs to a family of enzymes that determine the terminal structure of glycans. Fut8 is widely conserved from Caenorhabditis elegans to humans, and its mutants have been reported in humans, mice, and zebrafish. Although mutants show various symptoms, such as spinal deformity and growth retardation, its effects on skeletal muscles are unknown. We aimed to elucidate the function of Fut8 in skeletal muscle using zebrafish and C2C12 cells for evaluation. We observed that most fut8a morphants died at 2 days post-fertilization (dpf) or in earlier developmental stages even at low concentrations of morpholino oligonucleotides (MOs). Mutant juveniles also had small body sizes, and abnormal myocepta and sarcomere structures, suggesting that Fut8a plays important roles in myogenesis. Moreover, treatment of C2C12 cells with 2-fluorofucose (2FF), a fucosylation inhibitor, during cell differentiation dramatically reduced the expression of myogenic genes, such as and other myogenic fusion genes, and inhibited myotube formation. These results indicate that Fut8 is an important factor in myogenesis, and myofusion in particular.
Topics: Humans; Animals; Mice; Zebrafish; Fucosyltransferases; Muscle Fibers, Skeletal; Glycosylation; Muscle Development
PubMed: 36611938
DOI: 10.3390/cells12010144 -
Experimental Cell Research Nov 2010Notch signaling has emerged as a key player in skeletal muscle development and regeneration. Simply stated, Notch signaling inhibits differentiation. Accordingly,... (Review)
Review
Notch signaling has emerged as a key player in skeletal muscle development and regeneration. Simply stated, Notch signaling inhibits differentiation. Accordingly, fine-tuning the pathway is essential for proper muscle homeostasis. This review will address various aspects of Notch signaling, including our current views of the core pathway, its effects in muscle, its interactions with other signaling pathways, and its relationship with ageing.
Topics: Animals; Humans; Muscle Development; Muscle, Skeletal; Receptors, Notch; Signal Transduction
PubMed: 20452344
DOI: 10.1016/j.yexcr.2010.05.002 -
Physiological Reviews Jan 2004Under normal circumstances, mammalian adult skeletal muscle is a stable tissue with very little turnover of nuclei. However, upon injury, skeletal muscle has the... (Review)
Review
Under normal circumstances, mammalian adult skeletal muscle is a stable tissue with very little turnover of nuclei. However, upon injury, skeletal muscle has the remarkable ability to initiate a rapid and extensive repair process preventing the loss of muscle mass. Skeletal muscle repair is a highly synchronized process involving the activation of various cellular responses. The initial phase of muscle repair is characterized by necrosis of the damaged tissue and activation of an inflammatory response. This phase is rapidly followed by activation of myogenic cells to proliferate, differentiate, and fuse leading to new myofiber formation and reconstitution of a functional contractile apparatus. Activation of adult muscle satellite cells is a key element in this process. Muscle satellite cell activation resembles embryonic myogenesis in several ways including the de novo induction of the myogenic regulatory factors. Signaling factors released during the regenerating process have been identified, but their functions remain to be fully defined. In addition, recent evidence supports the possible contribution of adult stem cells in the muscle regeneration process. In particular, bone marrow-derived and muscle-derived stem cells contribute to new myofiber formation and to the satellite cell pool after injury.
Topics: Animals; Cell Differentiation; Growth Substances; Humans; Muscle Development; Muscle, Skeletal; Regeneration; Satellite Cells, Skeletal Muscle; Signal Transduction; Stem Cells
PubMed: 14715915
DOI: 10.1152/physrev.00019.2003 -
Experimental Cell Research Nov 2010Branchiomeric craniofacial muscles control feeding, breathing and facial expression. These muscles differ on multiple counts from all other skeletal muscles and... (Review)
Review
Branchiomeric craniofacial muscles control feeding, breathing and facial expression. These muscles differ on multiple counts from all other skeletal muscles and originate in a progenitor cell population in pharyngeal mesoderm characterized by a common genetic program with an adjacent population of cardiac progenitor cells, the second heart field, that gives rise to much of the heart. The transcription factors and signaling molecules that trigger the myogenic program at sites of branchiomeric muscle formation are correspondingly distinct from those in somite-derived muscle progenitor cells. Here new insights into the regulatory hierarchies controlling branchiomeric myogenesis are discussed. Differences in embryological origin are reflected in the lineage, transcriptional program and proliferative and differentiation properties of branchiomeric muscle satellite cells. These recent findings have important implications for our understanding of the diverse myogenic strategies operative both in the embryo and adult and are of direct biomedical relevance to deciphering the mechanisms underlying the cause and progression of muscle restricted myopathies.
Topics: Animals; Embryo, Mammalian; Facial Muscles; Humans; Muscle Development
PubMed: 20457151
DOI: 10.1016/j.yexcr.2010.04.029 -
Nature Reviews. Genetics Aug 2008The molecular, genetic and cellular bases for skeletal muscle growth and regeneration have been recently documented in a number of vertebrate species. These studies... (Review)
Review
The molecular, genetic and cellular bases for skeletal muscle growth and regeneration have been recently documented in a number of vertebrate species. These studies highlight the role of transient subcompartments of the early somite as a source of distinct waves of myogenic precursors. Individual myogenic progenitor populations undergo a complex series of cell rearrangements and specification events in different regions of the body, all of which are controlled by distinct gene regulatory networks. Collectively, these studies have opened a window into the morphogenetic and molecular bases of the different phases of vertebrate myogenesis, from embryo to adult.
Topics: Animals; Embryo, Mammalian; Embryo, Nonmammalian; Head; Heart; Humans; Models, Biological; Muscle Development; Muscles; Organ Specificity; RNA, Messenger; Vertebrates
PubMed: 18636072
DOI: 10.1038/nrg2369 -
ELife Nov 2023In vitro culture systems that structurally model human myogenesis and promote PAX7 myogenic progenitor maturation have not been established. Here we report that human...
In vitro culture systems that structurally model human myogenesis and promote PAX7 myogenic progenitor maturation have not been established. Here we report that human skeletal muscle organoids can be differentiated from induced pluripotent stem cell lines to contain paraxial mesoderm and neuromesodermal progenitors and develop into organized structures reassembling neural plate border and dermomyotome. Culture conditions instigate neural lineage arrest and promote fetal hypaxial myogenesis toward limb axial anatomical identity, with generation of sustainable uncommitted PAX7 myogenic progenitors and fibroadipogenic (PDGFRa+) progenitor populations equivalent to those from the second trimester of human gestation. Single-cell comparison to human fetal and adult myogenic progenitor /satellite cells reveals distinct molecular signatures for non-dividing myogenic progenitors in activated (//) and dormant (//) states. Our approach provides a robust 3D in vitro developmental system for investigating muscle tissue morphogenesis and homeostasis.
Topics: Humans; Muscle, Skeletal; Cell Differentiation; Fetus; Satellite Cells, Skeletal Muscle; Muscle Development; PAX7 Transcription Factor
PubMed: 37963071
DOI: 10.7554/eLife.87081 -
Journal of Animal Science Nov 2022Although it has long been known that growth media withdrawal is a prerequisite for myoblast differentiation and fusion, the underpinning molecular mechanism remains...
Although it has long been known that growth media withdrawal is a prerequisite for myoblast differentiation and fusion, the underpinning molecular mechanism remains somewhat elusive. Using isolated porcine muscle satellite cells (SCs) as the model, we show elevated O-GlcNAcylation by O-GlcNAcase (OGA) inhibition impaired SC differentiation (D5 P < 0.0001) but had unnoticeable impacts on SC proliferation. To explore the mechanism of this phenotype, we examined the expression of the transcription factor myogenin, a master switch of myogenesis, and found its expression was downregulated by elevated O-GlcNAcylation. Because insulin/IGF-1/Akt axis is a strong promoter of myoblast fusion, we measured the phosphorylated Akt and found that hyper O-GlcNAcylation inhibited Akt phosphorylation, implying OGA inhibition may also work through interfering with this critical differentiation-promoting pathway. In contrast, inhibition of O-GlcNAc transferase (OGT) by its specific inhibitor had little impact on either myoblast proliferation or differentiation (P > 0.05). To confirm these in vitro findings, we used chemical-induced muscle injury in the pig as a model to study muscle regenerative myogenesis and showed how O-GlcNAcylation functions in this process. We show a significant decrease in muscle fiber cross sectional area (CSA) when OGA is inhibited (P < 0.05), compared to nondamaged muscle, and a significant decrease compared to control and OGT inhibited muscle (P < 0.05), indicating a significant impairment in porcine muscle regeneration in vivo. Together, the in vitro and in vivo data suggest that O-GlcNAcylation may serve as a nutrient sensor during SC differentiation by gauging cellular nutrient availability and translating these signals into cellular responses. Given the importance of nutrition availability in lean muscle growth, our findings may have significant implications on how muscle growth is regulated in agriculturally important animals.
Topics: Animals; Swine; Proto-Oncogene Proteins c-akt; Muscle Development; Myoblasts; Cell Differentiation; Phosphorylation
PubMed: 36219104
DOI: 10.1093/jas/skac326 -
Molekuliarnaia Biologiia 2016Skeletal myogenesis has been extensively studied at both morphological and molecular levels. This review considers the main stages of embryonic skeletal myogenesis and... (Review)
Review
Skeletal myogenesis has been extensively studied at both morphological and molecular levels. This review considers the main stages of embryonic skeletal myogenesis and myogenic factors that trigger their initiation, focusing on specific protein interactions involved in somitic myogenesis, head myogenesis, and limb myogenesis. The second part of the review describes the role of noncoding RNAs (microRNAs and long noncoding RNAs) in myogenesis. This information is of particular interest, because regulation of cell processes by noncoding RNAs is an actively developing field of molecular biology. Knowledge of mechanisms of skeletal myogenesis is of applied significance. Various transcription factors, noncoding RNAs, and other myogenic regulators can be employed in the induction of myogenic reprogramming in stem cells and differentiated somatic cells. Current trends and strategies in the field of skeletal myogenic reprogramming are discussed in the last part of the review.
Topics: Animals; Cell Differentiation; Gene Expression Regulation, Developmental; Mammals; MicroRNAs; Muscle Development; Muscle, Skeletal; Myogenic Regulatory Factors; RNA, Long Noncoding
PubMed: 27239841
DOI: 10.7868/S0026898416010079 -
Expert Opinion on Biological Therapy Apr 2017The diseased host milieu, such as endothelial dysfunction (ED), decreased NO bioavailability, and ischemic/inflammatory post-MI environment, hamper the clinical success... (Review)
Review
The diseased host milieu, such as endothelial dysfunction (ED), decreased NO bioavailability, and ischemic/inflammatory post-MI environment, hamper the clinical success of existing cardiac regenerative therapies. Area covered: In this article, current strategies including pharmacological and nonpharmacological approaches for improving the diseased host milieu are reviewed. Specifically, the authors provide focus on: i) the mechanism of ED in patients with cardiovascular diseases, ii) the current results of ED improving strategies in pre-clinical and clinical studies, and iii) the use of biomaterials as a novel modulator in damaged post-MI environment. Expert opinion: Adjunct therapies which improve host endothelial function have demonstrated promising outcomes, potentially overcoming disappointing results of cell therapy in human studies. In the future, elucidation of the interactions between the host tissue and therapeutic agents, as well as downstream signaling pathways, will be the next challenges in enhancing regenerative therapy. More careful investigations are also required to establish these agents' safety and efficacy for wide usage in humans.
Topics: Animals; Arteries; Biocompatible Materials; Cell- and Tissue-Based Therapy; Heart; Humans; Muscle Development; Myocardial Infarction; Neovascularization, Physiologic; Regeneration; Vascular Diseases
PubMed: 28274146
DOI: 10.1080/14712598.2017.1293038