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Journal of Cachexia, Sarcopenia and... Feb 2022Circular RNAs (circRNAs) represent a novel class of non-coding RNAs formed by a covalently closed loop and play crucial roles in many biological processes. Several...
BACKGROUND
Circular RNAs (circRNAs) represent a novel class of non-coding RNAs formed by a covalently closed loop and play crucial roles in many biological processes. Several circRNAs associated with myogenesis have been reported. However, the dynamic expression, function, and mechanism of circRNAs during myogenesis and skeletal muscle development are largely unknown.
METHODS
Strand-specific RNA-sequencing (RNA-seq) and microarray datasets were used to profile the dynamic circRNAome landscape during skeletal muscle development and myogenic differentiation. Bioinformatics analyses were used to characterize the circRNAome and identify candidate circRNAs associated with myogenesis. Bulk and single-cell RNA-seq were performed to identify the downstream genes and pathways of circFgfr2. The primary myoblast cells, C2C12 cells, and animal model were used to assess the function and mechanism of circFgfr2 in myogenesis and muscle regeneration in vitro or in vivo by RT-qPCR, western blotting, dual-luciferase activity assay, RNA immunoprecipitation, RNA fluorescence in situ hybridization, and chromatin immunoprecipitation.
RESULTS
We profiled the dynamic circRNAome in pig skeletal muscle across 27 developmental stages and detected 52 918 high-confidence circRNAs. A total of 2916 of these circRNAs are conserved across human, mouse, and pig, including four circRNAs (circFgfr2, circQrich1, circMettl9, and circCamta1) that were differentially expressed (|log fold change| > 1 and adjusted P value < 0.05) in various myogenesis systems. We further focused on a conserved circRNA produced from the fibroblast growth factor receptor 2 (Fgfr2) gene, termed circFgfr2, which was found to inhibit myoblast proliferation and promote differentiation and skeletal muscle regeneration. Mechanistically, circFgfr2 acted as a sponge for miR-133 to regulate the mitogen-activated protein kinase kinase kinase 20 (Map3k20) gene and JNK/MAPK pathway. Importantly, transcription factor Kruppel like factor 4 (Klf4), the downstream target of the JNK/MAPK pathway, directly bound to the promoter of circFgfr2 and affected its expression via an miR-133/Map3k20/JNK/Klf4 auto-regulatory feedback loop. RNA binding protein G3BP stress granule assembly factor 1 (G3bp1) inhibited the biogenesis of circFgfr2.
CONCLUSIONS
The present study provides a comprehensive circRNA resource for skeletal muscle study. The functional and mechanistic analysis of circFgfr2 uncovered a circRNA-mediated auto-regulatory feedback loop regulating myogenesis and muscle regeneration, which provides new insight to further understand the regulatory mechanism of circRNAs.
Topics: Animals; DNA Helicases; Feedback; In Situ Hybridization, Fluorescence; Mice; Muscle Development; Muscle, Skeletal; Poly-ADP-Ribose Binding Proteins; RNA Helicases; RNA Recognition Motif Proteins; Regeneration; Swine
PubMed: 34811940
DOI: 10.1002/jcsm.12859 -
Cells Aug 2019Skeletal muscle myogenesis and injury-induced muscle regeneration contribute to muscle formation and maintenance. As myogenic stem cells, skeletal muscle satellite... (Review)
Review
Skeletal muscle myogenesis and injury-induced muscle regeneration contribute to muscle formation and maintenance. As myogenic stem cells, skeletal muscle satellite cells have the ability to proliferate, differentiate and self-renew, and are involved in muscle formation and muscle injury repair. Accumulating evidence suggests that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are widely involved in the regulation of gene expression during skeletal muscle myogenesis, and their abnormal expression is associated with a variety of muscle diseases. From the perspective of the molecular mechanism and mode of action of ncRNAs in myogenesis, this review aims to summarize the role of ncRNAs in skeletal muscle satellite cells' myogenic differentiation and in muscle disease, and systematically analyze the mechanism of ncRNAs in skeletal muscle development. This work will systematically summarize the role of ncRNAs in myogenesis and provide reference targets for the treatment of various muscle diseases, such as muscle dystrophy, atrophy and aberrant hypertrophy.
Topics: Animals; Humans; Muscle Development; Muscular Diseases; RNA, Untranslated; Satellite Cells, Skeletal Muscle
PubMed: 31461973
DOI: 10.3390/cells8090988 -
Current Opinion in Clinical Nutrition... May 2010Skeletal muscle development serves as a paradigm for cell lineage specification and cell differentiation. Adult skeletal muscle has high regenerative capacity, with... (Review)
Review
PURPOSE OF REVIEW
Skeletal muscle development serves as a paradigm for cell lineage specification and cell differentiation. Adult skeletal muscle has high regenerative capacity, with satellite cells the primary source of this capability. The present review describes recent findings on developmental and adult myogenesis with emphasis on emerging distinctions between various muscle groups and stages of myogenesis.
RECENT FINDINGS
Muscle progenitors of the body are derived from multipotent cells of the dermomyotome and express the transcription factors Pax3 and Pax7. These cells self-renew or induce expression of myogenic regulatory factors (MRFs) and differentiate. The roles of Pax3, Pax7 and specific myogenic regulatory factor progenitor populations in trunk and limb myogenesis have been identified through cell ablation in the mouse. Various head muscles and associated satellite cells have differing developmental origins, and rely on distinct combinations of transcriptional regulators, than trunk and limb muscles. Several genetic and sorting protocols demonstrate that satellite cells are heterogeneous with some possessing stem cell properties; the relative roles of lineage and niche in these properties are being explored. Although cellular mechanisms of developmental, postnatal and adult regenerative myogenesis are thought to be similar, recent studies reveal distinct genetic requirements for embryonic, fetal, postnatal and adult regenerative myogenesis.
SUMMARY
Genetic determinants of formation or repair of various muscles during different stages of myogenesis are unexpectedly diverse. Future studies should illuminate these differences, as well as mechanisms that underlie stem cell properties of satellite cells.
Topics: Animals; Cell Differentiation; Gene Expression Regulation; Muscle Development; Muscle, Skeletal; Myogenic Regulatory Factors; PAX3 Transcription Factor; PAX7 Transcription Factor; Paired Box Transcription Factors; Regeneration; Satellite Cells, Skeletal Muscle; Stem Cells
PubMed: 20098319
DOI: 10.1097/MCO.0b013e328336ea98 -
Biochimica Et Biophysica Acta Aug 2006Important functions in myogenesis have been proposed for FGF6, a member of the fibroblast growth factor family accumulating almost exclusively in the myogenic lineage.... (Review)
Review
Important functions in myogenesis have been proposed for FGF6, a member of the fibroblast growth factor family accumulating almost exclusively in the myogenic lineage. However, the analyses of Fgf6 (-/-) mutant mice gave contradictory results and the role of FGF6 during myogenesis remained largely unclear. Recent reports support the concept that FGF6 has a dual function in muscle regeneration, stimulating myoblast proliferation/migration and muscle differentiation/hypertrophy in a dose-dependent manner. The alternative use of distinct signaling pathways recruiting either FGFR1 or FGFR4 might explain the dual role of FGF6 in myogenesis. A role for FGF6 in the maintenance of a reserve pool of progenitor cells in the skeletal muscle has been also strongly suggested. The aim of this review is to summarize our knowledge on the involvement of FGF6 in myogenesis.
Topics: Animals; Cell Differentiation; Fibroblast Growth Factor 6; Gene Expression; Hypertrophy; Mice; Mice, Knockout; Muscle Development; Muscles; Phenotype; Proto-Oncogene Proteins; Receptors, Fibroblast Growth Factor; Regeneration; Signal Transduction; Stem Cells
PubMed: 16875743
DOI: 10.1016/j.bbamcr.2006.06.005 -
Seminars in Cell & Developmental Biology Dec 2017Myogenesis is a highly orchestrated, complex developmental process by which cell lineages that are mesodermal in origin generate differentiated multinucleate muscle... (Review)
Review
Myogenesis is a highly orchestrated, complex developmental process by which cell lineages that are mesodermal in origin generate differentiated multinucleate muscle cells as a final product. Considerable insight into the process of myogenesis has been obtained for the embryonic development of the larval muscles of Drosophila. More recently, the postembryonic development of the muscles of the adult fly has become a focus of experimental investigation of myogenesis since specific flight muscles of the fly manifest remarkable similarities to vertebrate muscles in their development and organization. In this review, we catalog some of the milestones in the study of myogenesis in the large adult-specific flight muscles of Drosophila. The identification of mesoderm-derived muscle stem cell lineages, the characterization of the symmetric and asymmetric divisions through which they produce adult-specific myoblasts, the multifaceted processes of myoblast fusion, and the unexpected discovery of quiescent satellite cells that can be activated by injury are discussed. Moreover, the finding that all of these processes incorporate a plethora of signaling interactions with other myogenic cells and with niche-like neighboring tissue is considered. Finally, we briefly point out possible future developments in the area of Drosophila myogenesis that may lead to of new avenues of genetic research into the roles of muscle stem cells in development, disease and aging.
Topics: Animals; Drosophila; Gene Expression Regulation, Developmental; Models, Genetic; Morphogenesis; Muscle Development; Muscle Fibers, Skeletal; Muscles; Myoblasts; Regeneration
PubMed: 29146144
DOI: 10.1016/j.semcdb.2017.11.017 -
PLoS Genetics Jun 2023Four SIX homeoproteins display a combinatorial expression throughout embryonic developmental myogenesis and they modulate the expression of the myogenic regulatory...
Four SIX homeoproteins display a combinatorial expression throughout embryonic developmental myogenesis and they modulate the expression of the myogenic regulatory factors. Here, we provide a deep characterization of their role in distinct mouse developmental territories. We showed, at the hypaxial level, that the Six1:Six4 double knockout (dKO) somitic precursor cells adopt a smooth muscle fate and lose their myogenic identity. At the epaxial level, we demonstrated by the analysis of Six quadruple KO (qKO) embryos, that SIX are required for fetal myogenesis, and for the maintenance of PAX7+ progenitor cells, which differentiated prematurely and are lost by the end of fetal development in qKO embryos. Finally, we showed that Six1 and Six2 are required to establish craniofacial myogenesis by controlling the expression of Myf5. We have thus described an unknown role for SIX proteins in the control of myogenesis at different embryonic levels and refined their involvement in the genetic cascades operating at the head level and in the genesis of myogenic stem cells.
Topics: Mice; Animals; Homeodomain Proteins; Cell Differentiation; Somites; Muscle Development; Gene Expression Regulation, Developmental; Muscle, Skeletal
PubMed: 37267426
DOI: 10.1371/journal.pgen.1010781 -
Cellular and Molecular Life Sciences :... May 2021The remodeling of the mitochondrial network is a critical process in maintaining cellular homeostasis and is intimately related to mitochondrial function. The interplay... (Review)
Review
The remodeling of the mitochondrial network is a critical process in maintaining cellular homeostasis and is intimately related to mitochondrial function. The interplay between the formation of new mitochondria (biogenesis) and the removal of damaged mitochondria (mitophagy) provide a means for the repopulation of the mitochondrial network. Additionally, mitochondrial fission and fusion serve as a bridge between biogenesis and mitophagy. In recent years, the importance of these processes has been characterised in multiple tissue- and cell-types, and under various conditions. In skeletal muscle, the robust remodeling of the mitochondrial network is observed, particularly after injury where large portions of the tissue/cell structures are damaged. The significance of mitochondrial remodeling in regulating skeletal muscle regeneration has been widely studied, with alterations in mitochondrial remodeling processes leading to incomplete regeneration and impaired skeletal muscle function. Needless to say, important questions related to mitochondrial remodeling and skeletal muscle regeneration still remain unanswered and require further investigation. Therefore, this review will discuss the known molecular mechanisms of mitochondrial network remodeling, as well as integrate these mechanisms and discuss their relevance in myogenesis and regenerating skeletal muscle.
Topics: Animals; Humans; Mitochondria; Muscle Development; Muscle, Skeletal; Regeneration
PubMed: 33751143
DOI: 10.1007/s00018-021-03807-9 -
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 Apr 2022MyoD, Myf5, myogenin, and MRF4 (also known as Myf6 or herculin) are myogenic regulatory factors (MRFs). MRFs are regarded as master transcription factors that are... (Review)
Review
MyoD, Myf5, myogenin, and MRF4 (also known as Myf6 or herculin) are myogenic regulatory factors (MRFs). MRFs are regarded as master transcription factors that are upregulated during myogenesis and influence stem cells to differentiate into myogenic lineage cells. In this review, we summarize MRFs, their regulatory factors, such as TLE3, NF-κB, and MRF target genes, including non-myogenic genes such as taste receptors. Understanding the function of MRFs and the physiology or pathology of satellite cells will contribute to the development of cell therapy and drug discovery for muscle-related diseases.
Topics: Muscle Development; Muscle, Skeletal; MyoD Protein; Myogenic Regulatory Factors; Stem Cells
PubMed: 35563799
DOI: 10.3390/cells11091493 -
Biomedicine & Pharmacotherapy =... May 2024Mammalian skeletal myogenesis is a complex process that allows precise control of myogenic cells' proliferation, differentiation, and fusion to form multinucleated,... (Review)
Review
Mammalian skeletal myogenesis is a complex process that allows precise control of myogenic cells' proliferation, differentiation, and fusion to form multinucleated, contractile, and functional muscle fibers. Typically, myogenic progenitors continue growth and division until acquiring a differentiated state, which then permanently leaves the cell cycle and enters terminal differentiation. These processes have been intensively studied using the skeletal muscle developing models in vitro and in vivo, uncovering a complex cellular intrinsic network during mammalian skeletal myogenesis containing transcription factors, translation factors, extracellular matrix, metabolites, and mechano-sensors. Examining the events and how they are knitted together will better understand skeletal myogenesis's molecular basis. This review describes various regulatory mechanisms and recent advances in myogenic cell proliferation and differentiation during mammalian skeletal myogenesis. We focus on significant cell cycle regulators, myogenic factors, and chromatin regulators impacting the coordination of the cell proliferation versus differentiation decision, which will better clarify the complex signaling underlying skeletal myogenesis.
Topics: Muscle Development; Cell Differentiation; Animals; Cell Proliferation; Humans; Muscle, Skeletal; Mammals; Signal Transduction; Myogenic Regulatory Factors
PubMed: 38583341
DOI: 10.1016/j.biopha.2024.116563