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Cold Spring Harbor Perspectives in... Feb 2012The genesis of skeletal muscle during embryonic development and postnatal life serves as a paradigm for stem and progenitor cell maintenance, lineage specification, and... (Review)
Review
The genesis of skeletal muscle during embryonic development and postnatal life serves as a paradigm for stem and progenitor cell maintenance, lineage specification, and terminal differentiation. An elaborate interplay of extrinsic and intrinsic regulatory mechanisms controls myogenesis at all stages of development. Many aspects of adult myogenesis resemble or reiterate embryonic morphogenetic episodes, and related signaling mechanisms control the genetic networks that determine cell fate during these processes. An integrative view of all aspects of myogenesis is imperative for a comprehensive understanding of muscle formation. This article provides a holistic overview of the different stages and modes of myogenesis with an emphasis on the underlying signals, molecular switches, and genetic networks.
Topics: Animals; Female; Humans; Muscle Development; Muscle Proteins; Muscle, Skeletal; Pregnancy; Stem Cells
PubMed: 22300977
DOI: 10.1101/cshperspect.a008342 -
Journal of Cachexia, Sarcopenia and... Dec 2022Human pluripotent stem cell-derived muscle models show great potential for translational research. Here, we describe developmentally inspired methods for the derivation...
BACKGROUND
Human pluripotent stem cell-derived muscle models show great potential for translational research. Here, we describe developmentally inspired methods for the derivation of skeletal muscle cells and their utility in skeletal muscle tissue engineering with the aim to model skeletal muscle regeneration and dystrophy in vitro.
METHODS
Key steps include the directed differentiation of human pluripotent stem cells to embryonic muscle progenitors followed by primary and secondary foetal myogenesis into three-dimensional muscle. To simulate Duchenne muscular dystrophy (DMD), a patient-specific induced pluripotent stem cell line was compared to a CRISPR/Cas9-edited isogenic control line.
RESULTS
The established skeletal muscle differentiation protocol robustly and faithfully recapitulates critical steps of embryonic myogenesis in two-dimensional and three-dimensional cultures, resulting in functional human skeletal muscle organoids (SMOs) and engineered skeletal muscles (ESMs) with a regeneration-competent satellite-like cell pool. Tissue-engineered muscle exhibits organotypic maturation and function (up to 5.7 ± 0.5 mN tetanic twitch tension at 100 Hz in ESM). Contractile performance could be further enhanced by timed thyroid hormone treatment, increasing the speed of contraction (time to peak contraction) as well as relaxation (time to 50% relaxation) of single twitches from 107 ± 2 to 75 ± 4 ms (P < 0.05) and from 146 ± 6 to 100 ± 6 ms (P < 0.05), respectively. Satellite-like cells could be documented as largely quiescent PAX7 cells (75 ± 6% Ki67 ) located adjacent to muscle fibres confined under a laminin-containing basal membrane. Activation of the engineered satellite-like cell niche was documented in a cardiotoxin injury model with marked recovery of contractility to 57 ± 8% of the pre-injury force 21 days post-injury (P < 0.05 compared to Day 2 post-injury), which was completely blocked by preceding irradiation. Absence of dystrophin in DMD ESM caused a marked reduction of contractile force (-35 ± 7%, P < 0.05) and impaired expression of fast myosin isoforms resulting in prolonged contraction (175 ± 14 ms, P < 0.05 vs. gene-edited control) and relaxation (238 ± 22 ms, P < 0.05 vs. gene-edited control) times. Restoration of dystrophin levels by gene editing rescued the DMD phenotype in ESM.
CONCLUSIONS
We introduce human muscle models with canonical properties of bona fide skeletal muscle in vivo to study muscle development, maturation, disease and repair.
Topics: Humans; Muscular Dystrophy, Duchenne; Muscle, Skeletal; Muscle Development; Satellite Cells, Skeletal Muscle; Muscle Fibers, Skeletal
PubMed: 36254806
DOI: 10.1002/jcsm.13094 -
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 -
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 -
Cell Proliferation Jul 2020Exosomes are membrane-bound extracellular vesicles that are produced in the endosomal compartment of most mammalian cell types and then released. Exosomes are effective... (Review)
Review
Exosomes are membrane-bound extracellular vesicles that are produced in the endosomal compartment of most mammalian cell types and then released. Exosomes are effective carriers for the intercellular material transfer of material that can influence a series of physiological and pathological processes in recipient cells. Among loaded cargoes, non-coding RNAs (ncRNAs) vary for the exosome-producing cell and its homeostatic state, and characterization of the biogenesis and secretion of exosomal ncRNAs and the functions of these ncRNAs in skeletal muscle myogenesis remain preliminary. In this review, we will describe what is currently known of exosome biogenesis, release and uptake of exosomal ncRNAs, as well as the varied functions of exosomal miRNAs in skeletal muscle myogenesis.
Topics: Animals; Exosomes; Humans; MicroRNAs; Muscle Development; Muscle, Skeletal
PubMed: 32578911
DOI: 10.1111/cpr.12857 -
Differentiation; Research in Biological... 2016Mesenchymal stem cells (MSCs) are multipotent cells that represent a promising source for regenerative medicine. MSCs are capable of osteogenic, chondrogenic, adipogenic... (Review)
Review
Mesenchymal stem cells (MSCs) are multipotent cells that represent a promising source for regenerative medicine. MSCs are capable of osteogenic, chondrogenic, adipogenic and myogenic differentiation. Efficacy of differentiated MSCs to regenerate cells in the injured tissues requires the ability to maintain the differentiation toward the desired cell fate. Since MSCs represent an attractive source for autologous transplantation, cellular and molecular signaling pathways and micro-environmental changes have been studied in order to understand the role of cytokines, chemokines, and transcription factors on the differentiation of MSCs. The differentiation of MSC into a mesenchymal lineage is genetically manipulated and promoted by specific transcription factors associated with a particular cell lineage. Recent studies have explored the integration of transcription factors, including Runx2, Sox9, PPARγ, MyoD, GATA4, and GATA6 in the differentiation of MSCs. Therefore, the overexpression of a single transcription factor in MSCs may promote trans-differentiation into specific cell lineage, which can be used for treatment of some diseases. In this review, we critically discussed and evaluated the role of transcription factors and related signaling pathways that affect the differentiation of MSCs toward adipocytes, chondrocytes, osteocytes, skeletal muscle cells, cardiomyocytes, and smooth muscle cells.
Topics: Adipogenesis; Animals; Cell Differentiation; Chondrogenesis; Humans; Mesenchymal Stem Cells; Muscle Development; Regenerative Medicine; Transcription Factors
PubMed: 27012163
DOI: 10.1016/j.diff.2016.02.005 -
The International Journal of... 2018Striated muscle is the most abundant tissue in the body of vertebrates and it forms, together with the skeleton, the locomotory system required both for movement and the... (Review)
Review
Striated muscle is the most abundant tissue in the body of vertebrates and it forms, together with the skeleton, the locomotory system required both for movement and the creation of the specific body shape of a species. Research on the embryonic development of muscles has a long tradition both in classical embryology and in molecular developmental biology. While the gene networks regulating muscle development have been discovered mostly in the mouse through genetics, our knowledge on cell lineages, muscle morphogenesis and tissue interactions regulating their formation is to a large extent based on the use of the avian model. This review highlights present knowledge of the development of skeletal muscle in vertebrate embryos. Special focus will be placed on the contributions from chicken and quail embryo model systems.
Topics: Animals; Cell Differentiation; Cell Lineage; Chick Embryo; Chickens; Electroporation; Embryonic Development; Mesoderm; Mice; Morphogenesis; Muscle Development; Quail; Signal Transduction; Somites; Stem Cells
PubMed: 29616720
DOI: 10.1387/ijdb.170312cm -
International Journal of Molecular... May 2022In vitro organoids derived from human pluripotent stem cells (hPSCs) have been developed as essential tools to study the underlying mechanisms of human development and...
In vitro organoids derived from human pluripotent stem cells (hPSCs) have been developed as essential tools to study the underlying mechanisms of human development and diseases owing to their structural and physiological similarity to corresponding organs. Despite recent advances, there are a few methodologies for three-dimensional (3D) skeletal muscle differentiation, which focus on the terminal differentiation into myofibers and investigate the potential of modeling neuromuscular disorders and muscular dystrophies. However, these methodologies cannot recapitulate the developmental processes and lack regenerative capacity. In this study, we developed a new method to differentiate hPSCs into a 3D human skeletal muscle organoid (hSkMO). This organoid model could recapitulate the myogenesis process and possesses regenerative capacities of sustainable satellite cells (SCs), which are adult muscle stem/progenitor cells capable of self-renewal and myogenic differentiation. Our 3D model demonstrated myogenesis through the sequential occurrence of multiple myogenic cell types from SCs to myocytes. Notably, we detected quiescent, non-dividing SCs throughout the hSkMO differentiation in long-term culture. They were activated and differentiated to reconstitute muscle tissue upon damage. Thus, hSkMOs can recapitulate human skeletal muscle development and regeneration and may provide a new model for studying human skeletal muscles and related diseases.
Topics: Cell Differentiation; Humans; Muscle Development; Muscle, Skeletal; Organoids; Pluripotent Stem Cells
PubMed: 35563499
DOI: 10.3390/ijms23095108 -
Redox Biology Apr 2022The regeneration of adult skeletal muscle after injury is primarily initiated by satellite cells (SCs), but the regulatory mechanisms of cells committed to myogenic...
The regeneration of adult skeletal muscle after injury is primarily initiated by satellite cells (SCs), but the regulatory mechanisms of cells committed to myogenic differentiation remain poorly explored. Small molecular selenoprotein K (SelK) plays crucial roles in the modulation of endoplasmic reticulum (ER) stress and against oxidative stress. Here, we first showed that SelK expression is activated in myogenic cells during differentiation both in vivo and in vitro. Meanwhile, loss of SelK delayed skeletal muscle regeneration, inhibited the development of myoblasts into myotubes, and was accompanied by reduced expression of myogenic regulatory factors (MRFs). Moreover, ER stress, intracellular reactive oxygen species (ROS), autophagy and apoptosis under myogenesis induction were more severe in SelK-deficient mice and cells than in the corresponding control groups. Supplementation with specific inhibitors to alleviate excessive ER stress or oxidative stress partly rescued the differentiation potential and formation of myotubes. Notably, we demonstrated that Self-mediated regulation of cellular redox status was primarily derived from its subsequent effects on ER stress. Together, our results suggest that SelK protects skeletal muscle from damage and is a crucial regulator of myogenesis.
Topics: Animals; Cell Differentiation; Mice; Muscle Development; Muscle Fibers, Skeletal; Muscle, Skeletal; Myoblasts; Selenoproteins
PubMed: 35144051
DOI: 10.1016/j.redox.2022.102255 -
Cell Reports Jan 2022The lipid droplet (LD) is a central hub for fatty acid metabolism in cells. Here we define the dynamics and explore the role of LDs in skeletal muscle satellite cells...
The lipid droplet (LD) is a central hub for fatty acid metabolism in cells. Here we define the dynamics and explore the role of LDs in skeletal muscle satellite cells (SCs), a stem cell population responsible for muscle regeneration. In newly divided SCs, LDs are unequally distributed in sister cells exhibiting asymmetric cell fates, as the LD cell self-renews while the LD cell commits to differentiation. When transplanted into regenerating muscles, LD cells outperform LD cells in self-renewal and regeneration in vivo. Pharmacological inhibition of LD biogenesis or genetic inhibition of LD catabolism through knockout of Pnpla2 (encoding ATGL, the rate-limiting enzyme for lipolysis) disrupts cell fate homeostasis and impairs the regenerative capacity of SCs. Dysfunction of Pnpla2-null SCs is associated with energy insufficiency and oxidative stress that can be partially rescued by antioxidant (N-acetylcysteine) treatment. These results establish a direct link between LD dynamics and stem cell fate determination.
Topics: Animals; Lipid Droplets; Mice; Muscle Development; Muscle, Skeletal; Regeneration; Satellite Cells, Skeletal Muscle
PubMed: 35045287
DOI: 10.1016/j.celrep.2021.110267