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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 -
Journal of Cell Science Aug 2016In aerobic organisms, oxygen is a critical factor for tissue and organ morphogenesis from embryonic development throughout the adult life. It regulates various... (Review)
Review
In aerobic organisms, oxygen is a critical factor for tissue and organ morphogenesis from embryonic development throughout the adult life. It regulates various intracellular pathways involved in cellular metabolism, proliferation, cell survival and fate. Organisms or tissues rapidly respond to changes in oxygen availability by activating complex signalling networks, which culminate in the control of mRNA translation and/or gene expression. This Commentary presents the effects of hypoxia during embryonic development, myoblasts and satellite cell proliferation and differentiation in vertebrates. We also outline the relationship between Notch, Wnt and growth factor signalling pathways, as well as the post-transcriptional regulation of myogenesis under conditions of hypoxia.
Topics: Animals; Cell Hypoxia; Gene Expression Regulation; Humans; Muscle Development; Myoblasts; Protein Biosynthesis; Signal Transduction
PubMed: 27505427
DOI: 10.1242/jcs.188904 -
Current Topics in Developmental Biology 2018The skeletal muscle lineage derives from the embryonic paraxial mesoderm (PM) which also gives rise to the axial skeleton, the dermis of the back, brown fat, meninges,... (Review)
Review
The skeletal muscle lineage derives from the embryonic paraxial mesoderm (PM) which also gives rise to the axial skeleton, the dermis of the back, brown fat, meninges, and endothelial cells. Direct conversion was pioneered in skeletal muscle with overexpression of the transcription factor MyoD which can convert fibroblasts to a muscle fate. In contrast, directed differentiation of skeletal muscle from pluripotent cells (PC) in vitro has proven to be very difficult compared to other lineages and has only been achieved recently. Experimental strategies recapitulating myogenesis in vitro from mouse and human PC (ES/iPS) have now been reported and all rely on early activation of Wnt signaling at the epiblast stage. This leads to induction of neuromesodermal progenitors that can subsequently be induced to a PM fate and to skeletal muscle. These protocols can efficiently produce fetal muscle fibers and immature satellite cells. These new in vitro systems now open the possibility to better understand human myogenesis and to develop in vitro disease models as well as cell therapy approaches.
Topics: Animals; Bone Morphogenetic Proteins; Cell Differentiation; Humans; Mesoderm; Models, Biological; Muscle Development; Stem Cells
PubMed: 29801528
DOI: 10.1016/bs.ctdb.2018.03.003 -
Comprehensive Physiology Jun 2016MicroRNAs (miRNAs) are a class of small noncoding RNAs highly conserved across species. miRNAs regulate gene expression posttranscriptionally by base pairing to... (Review)
Review
MicroRNAs (miRNAs) are a class of small noncoding RNAs highly conserved across species. miRNAs regulate gene expression posttranscriptionally by base pairing to complementary sequences mainly in the 3'-untranslated region of their target mRNAs to induce mRNA cleavage and translational repression. Thousands of miRNAs have been identified in human and their function has been linked to the regulation of both physiological and pathological processes. The skeletal muscle is the largest human organ responsible for locomotion, posture, and body metabolism. Several conditions such as aging, immobilization, exercise, and diet are associated with alterations in skeletal muscle structure and function. The genetic and molecular pathways that regulate muscle development, function, and regeneration as well as muscular disease have been well established in past decades. In recent years, numerous studies have underlined the importance of miRNAs in the control of skeletal muscle development and function, through its effects on several biological pathways critical for skeletal muscle homeostasis. Furthermore, it has become clear that alteration of the expression of many miRNAs or genetic mutations of miRNA genes is associated with changes on myogenesis and on progression of several skeletal muscle diseases. The present review provides an overview of the current studies and recent progress in elucidating the complex role exerted by miRNAs on skeletal muscle physiology and pathology. © 2016 American Physiological Society. Compr Physiol 6:1279-1294, 2016.
Topics: Aging; Cell Differentiation; Exercise; Gene Expression Regulation; Humans; MicroRNAs; Muscle Development; Muscle, Skeletal; Muscular Diseases; Organelle Biogenesis; Regeneration
PubMed: 27347893
DOI: 10.1002/cphy.c150041 -
Progress in Molecular Biology and... Jan 2018Wnt is a family of signaling molecules involved in embryogenesis, adult tissue repair, and cancer. They activate canonical and noncanonical Wnt signaling cascades in... (Review)
Review
Wnt is a family of signaling molecules involved in embryogenesis, adult tissue repair, and cancer. They activate canonical and noncanonical Wnt signaling cascades in target cells. Several studies, within the last decades, showed that several Wnt ligands are involved in myogenesis and both canonical and noncanonical Wnt pathways regulate muscle formation and the maintenance of adult tissue homeostasis. In this review, we provide a comprehensive overview of the roles of Wnt signaling during muscle development and an updated description of Wnt functions during muscle repair. Lastly, we discuss the crosstalk between Wnt and TGFβ signaling pathways in skeletal muscle.
Topics: Animals; Cell Differentiation; Cell Proliferation; Homeostasis; Humans; Muscle Development; Muscle, Skeletal; Regeneration; Wnt Proteins; Wnt Signaling Pathway
PubMed: 29389515
DOI: 10.1016/bs.pmbts.2017.11.026 -
Experimental Cell Research Feb 2022Human pluripotent stem cells (hPSCs) provide a human model for developmental myogenesis, disease modeling and development of therapeutics. Differentiation of hPSCs into... (Review)
Review
Human pluripotent stem cells (hPSCs) provide a human model for developmental myogenesis, disease modeling and development of therapeutics. Differentiation of hPSCs into muscle stem cells has the potential to provide a cell-based therapy for many skeletal muscle wasting diseases. This review describes the current state of hPSCs towards recapitulating human myogenesis ex vivo, considerations of stem cell and progenitor cell state as well as function for future use of hPSC-derived muscle cells in regenerative medicine.
Topics: Cell Differentiation; Humans; Models, Biological; Muscle Development; Muscle, Skeletal; Myoblasts, Skeletal; PAX7 Transcription Factor; Pluripotent Stem Cells; Satellite Cells, Skeletal Muscle
PubMed: 34973262
DOI: 10.1016/j.yexcr.2021.112990 -
Gene Aug 2018MicroRNAs (miRNAs) are small (about 22 nucleotides) noncoding RNAs, which were highly conserved among mammals. They have ushered in a new era in molecular biology over... (Review)
Review
MicroRNAs (miRNAs) are small (about 22 nucleotides) noncoding RNAs, which were highly conserved among mammals. They have ushered in a new era in molecular biology over twenty years. They can negatively regulate gene expression at the posttranscriptional level through the principle of complementary base pairing with the 3' untranslated region (UTR) of their target mRNAs and induce their degradation. They involve in tissue morphogenesis, cellular processes like apoptosis, and major signaling pathways. Previous studies have promoted our understanding that miRNAs play an important role in myogenesis and have a big impact on muscle mass, muscle fiber type and muscle diseases. Many researchers have provided evidence of the involvement of muscle-specific and enriched miRNAs in the individual stages of skeletal muscle development as well as of their significant influence on muscle metabolism during quiescence, proliferation, differentiation and regeneration. Here, we focus on the microRNAs that related to the development of skeletal muscle. For example, some microRNAs are upregulated in differentiated skeletal muscle and can promote differentiation, like, miR-1, miR-24, miR-26a, miR-181 and miR-206. However, some microRNAs highly expressed in proliferating myoblasts, downregulated in differentiated and could inhibit differentiation, like MiR-221 and miR-222. Some others not only promote skeletal muscle proliferation, but also promote differentiation, like miR-214. Studying the miRNAs' regulatory mechanisms in skeletal development will help us know more about the knowledge of miRNAs in muscle developmental biology and make us learn more about involved signal pathway.
Topics: Animals; Cell Differentiation; Cell Proliferation; Gene Expression Regulation; MicroRNAs; Muscle Development; Muscle, Skeletal; Myoblasts, Skeletal
PubMed: 29775754
DOI: 10.1016/j.gene.2018.05.039 -
Current Topics in Developmental Biology 2018Skeletal muscle regeneration is an efficient stem cell-based repair system that ensures healthy musculature. For this repair system to function continuously throughout... (Review)
Review
Skeletal muscle regeneration is an efficient stem cell-based repair system that ensures healthy musculature. For this repair system to function continuously throughout life, muscle stem cells must contribute to the process of myofiber repair as well as repopulation of the stem cell niche. The decision made by the muscle stem cells to commit to the muscle repair or to remain a stem cell depends upon patterns of gene expression, a process regulated at the epigenetic level. Indeed, it is well accepted that dynamic changes in epigenetic landscapes to control DNA accessibility and expression is a critical component during myogenesis for the effective repair of damaged muscle. Changes in the epigenetic landscape are governed by various posttranslational histone tail modifications, nucleosome repositioning, and DNA methylation events which collectively allow the control of changes in transcription networks during transitions of satellite cells from a dormant quiescent state toward terminal differentiation. This chapter focuses upon the specific epigenetic changes that occur during muscle stem cell-mediated regeneration to ensure myofiber repair and continuity of the stem cell compartment. Furthermore, we explore open questions in the field that are expected to be important areas of exploration as we move toward a more thorough understanding of the epigenetic mechanism regulating muscle regeneration.
Topics: Adult; Animals; Cell Differentiation; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Humans; Muscle Development; Muscle, Skeletal; Regeneration; Satellite Cells, Skeletal Muscle
PubMed: 29305001
DOI: 10.1016/bs.ctdb.2017.08.002 -
Ageing Research Reviews May 2021Mitochondria are highly dynamic organelles capable of adapting their network, morphology, and function, playing a role in oxidative phosphorylation and many cellular... (Review)
Review
Mitochondria are highly dynamic organelles capable of adapting their network, morphology, and function, playing a role in oxidative phosphorylation and many cellular processes in most cell types. Skeletal muscle is a very plastic tissue, subjected to many morphological changes following diverse stimuli, such as during myogenic differentiation and regenerative myogenesis. For some time now, mitochondria have been reported to be involved in myogenesis by promoting a bioenergetic remodeling and assisting myoblasts in surviving the process. However, not much is known about the interplay between mitochondrial quality control and myogenic differentiation. Sestrin2 (SESN2) is a well described regulator of autophagy and antioxidant responses and has been gaining attention due to its role in aging-associated pathologies and redox signaling promoted by reactive oxygen species (ROS) in many tissues. Current evidence involving SESN2-associated pathways suggest that it can act as a potential regulator of mitochondrial quality control following induction by ROS under stress conditions, such as during myogenesis. Yet, there are no studies directly assessing SESN2 involvement in myogenic differentiation. This review provides novel insights pertaining the involvement of SESN2 in myogenic differentiation by analyzing the interactions between ROS and mitochondrial remodeling.
Topics: Cell Differentiation; Mitochondria; Muscle Development; Myoblasts; Reactive Oxygen Species
PubMed: 33626408
DOI: 10.1016/j.arr.2021.101309 -
Cellular and Molecular Life Sciences :... Aug 2022Although 5-methylcytosine (mC) has been identified as a novel and abundant mRNA modification and associated with energy metabolism, its regulation function in adipose...
Although 5-methylcytosine (mC) has been identified as a novel and abundant mRNA modification and associated with energy metabolism, its regulation function in adipose tissue and skeletal muscle is still limited. This study aimed at investigating the effect of mRNA mC on adipogenesis and myogenesis using Jinhua pigs (J), Yorkshire pigs (Y) and their hybrids Yorkshire-Jinhua pigs (YJ). We found that Y grow faster than J and YJ, while fatness-related characteristics observed in Y were lower than those of J and YJ. Besides, total mRNA mC levels and expression rates of NSUN2 were higher both in backfat layer (BL) and longissimus dorsi muscle (LDM) of Y compared to J and YJ, suggesting that higher mRNA mC levels positively correlate with lower fat and higher muscle mass. RNA bisulfite sequencing profiling of mC revealed tissue-specific and dynamic features in pigs. Functionally, hyper-methylated mC-containing genes were enriched in pathways linked to impaired adipogenesis and enhanced myogenesis. In in vitro, mC inhibited lipid accumulation and promoted myogenic differentiation. Furthermore, YBX2 and SMO were identified as mC targets. Mechanistically, YBX2 and SMO mRNAs with mC modification were recognized and exported into the cytoplasm from the nucleus by ALYREF, thus leading to increased YBX2 and SMO protein expression and thereby inhibiting adipogenesis and promoting myogenesis, respectively. Our work uncovered the critical role of mRNA mC in regulating adipogenesis and myogenesis via ALYREF-mC-YBX2 and ALYREF-mC-SMO manners, providing a potential therapeutic target in the prevention and treatment of obesity, skeletal muscle dysfunction and metabolic disorder diseases.
Topics: Adipogenesis; Animals; Muscle Development; RNA Transport; RNA, Messenger; RNA-Binding Proteins; Swine
PubMed: 35962235
DOI: 10.1007/s00018-022-04474-0