scholarly journals Sustained expression of HeyL is critical for the proliferation of muscle stem cells in overloaded muscle

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Sumiaki Fukuda ◽  
Akihiro Kaneshige ◽  
Takayuki Kaji ◽  
Yu-taro Noguchi ◽  
Yusei Takemoto ◽  
...  
Keyword(s):  
Stem Cells ◽  
Basal Lamina ◽  
Satellite Cells ◽  
Knockout Mice ◽  
Muscle Stem Cells ◽  
Muscle Satellite Cells ◽  
Effector Gene ◽  
Injury Model ◽  
Myod Expression

In overloaded and regenerating muscle, the generation of new myonuclei depends on muscle satellite cells (MuSCs). Because MuSC behaviors in these two environments have not been considered separately, MuSC behaviors in overloaded muscle remain unexamined. Here, we show that most MuSCs in overloaded muscle, unlike MuSCs in regenerating muscle, proliferate in the absence of MyoD expression. Mechanistically, MuSCs in overloaded muscle sustain the expression of Heyl, a Notch effector gene, to suppress MyoD expression, which allows effective MuSC proliferation on myofibers and beneath the basal lamina. Although Heyl-knockout mice show no impairment in an injury model, in a hypertrophy model, their muscles harbor fewer new MuSC-derived myonuclei due to increased MyoD expression and diminished proliferation, which ultimately causes blunted hypertrophy. Our results show that sustained HeyL expression is critical for MuSC proliferation specifically in overloaded muscle, and thus indicate that the MuSC-proliferation mechanism differs in overloaded and regenerating muscle.

scholarly journals Identification and functional characterization of muscle satellite cells in Drosophila

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Dhananjay Chaturvedi ◽  
Heinrich Reichert ◽  
Rajesh D Gunage ◽  
K VijayRaghavan
Keyword(s):  
Stem Cells ◽  
Muscle Fiber ◽  
Satellite Cells ◽  
Genetic Model ◽  
Functional Characterization ◽  
Model Systems ◽  
Muscle Stem Cells ◽  
Muscle Satellite Cells ◽  
Adult Muscle ◽  
Functional Features

Work on genetic model systems such as Drosophila and mouse has shown that the fundamental mechanisms of myogenesis are remarkably similar in vertebrates and invertebrates. Strikingly, however, satellite cells, the adult muscle stem cells that are essential for the regeneration of damaged muscles in vertebrates, have not been reported in invertebrates. In this study, we show that lineal descendants of muscle stem cells are present in adult muscle of Drosophila as small, unfused cells observed at the surface and in close proximity to the mature muscle fibers. Normally quiescent, following muscle fiber injury, we show that these cells express Zfh1 and engage in Notch-Delta-dependent proliferative activity and generate lineal descendant populations, which fuse with the injured muscle fiber. In view of strikingly similar morphological and functional features, we consider these novel cells to be the Drosophila equivalent of vertebrate muscle satellite cells.

scholarly journals Identification and Functional Characterization of Muscle Satellite Cells in Drosophila

2016 ◽  
Author(s):  
Dhananjay Chaturvedi ◽  
Heinrich Reichert ◽  
Rajesh Gunage ◽  
K. VijayRaghavan
Keyword(s):  
Stem Cells ◽  
Muscle Fiber ◽  
Satellite Cells ◽  
Genetic Model ◽  
Functional Characterization ◽  
Model Systems ◽  
Muscle Stem Cells ◽  
Muscle Satellite Cells ◽  
Adult Muscle ◽  
Functional Features

AbstractWork on genetic model systems such as Drosophila and mouse has shown that the fundamental mechanisms of myogenesis are remarkably similar in vertebrates and invertebrates. Strikingly however, satellite cells, the adult muscle stem cells that are essential for the regeneration of damaged muscles in vertebrates, have not been reported in invertebrates. In this study we show that lineal descendants of muscle stem cells are present in adult muscle of Drosophila as small, unfused cells located superficially and in close proximity to the mature muscle fibers. Normally quiescent, following muscle fiber injury, we show that these cells express Zfh1- cells and engage in Notch-Delta dependent proliferative activity and generate lineal descendant populations, which fuse with the injured muscle fiber. In view of strikingly similar morphological and functional features, we consider these novel cells to be the Drosophila equivalent of vertebrate muscle satellite cells.

scholarly journals The role of Pitx2 and Pitx3 in muscle stem cells gives new insights into P38α MAP kinase and redox regulation of muscle regeneration

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Aurore L'honoré ◽  
Pierre-Henri Commère ◽  
Elisa Negroni ◽  
Giorgia Pallafacchina ◽  
Bertrand Friguet ◽  
...  
Keyword(s):  
Stem Cells ◽  
Map Kinase ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Redox Regulation ◽  
Primary Cultures ◽  
Rapid Expansion ◽  
Skeletal Muscle Regeneration ◽  
Muscle Stem Cells ◽  
P38α Map Kinase

Skeletal muscle regeneration depends on satellite cells. After injury these muscle stem cells exit quiescence, proliferate and differentiate to regenerate damaged fibres. We show that this progression is accompanied by metabolic changes leading to increased production of reactive oxygen species (ROS). Using Pitx2/3 single and double mutant mice that provide genetic models of deregulated redox states, we demonstrate that moderate overproduction of ROS results in premature differentiation of satellite cells while high levels lead to their senescence and regenerative failure. Using the ROS scavenger, N-Acetyl-Cysteine (NAC), in primary cultures we show that a physiological increase in ROS is required for satellite cells to exit the cell cycle and initiate differentiation through the redox activation of p38α MAP kinase. Subjecting cultured satellite cells to transient inhibition of P38α MAP kinase in conjunction with NAC treatment leads to their rapid expansion, with striking improvement of their regenerative potential in grafting experiments.

scholarly journals Satellite Cells CD44 Positive Drive Muscle Regeneration in Osteoarthritis Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Manuel Scimeca ◽  
Elena Bonanno ◽  
Eleonora Piccirilli ◽  
Jacopo Baldi ◽  
Alessandro Mauriello ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Stem Cells ◽  
Transmission Electron Microscopy ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Bone Diseases ◽  
Mineral Density ◽  
Muscle Stem Cells ◽  
Age Related ◽  
Transmission Electron

Age-related bone diseases, such as osteoarthritis and osteoporosis, are strongly associated with sarcopenia and muscle fiber atrophy. In this study, we analyzed muscle biopsies in order to demonstrate that, in osteoarthritis patients, both osteophytes formation and regenerative properties of muscle stem cells are related to the same factors. In particular, thanks to immunohistochemistry, transmission electron microscopy, and immunogold labeling we investigated the role of BMP-2 in muscle stem cells activity. In patients with osteoarthritis both immunohistochemistry and transmission electron microscopy allowed us to note a higher number of CD44 positive satellite muscle cells forming syncytium. Moreover, the perinuclear and cytoplasmic expression of BMP-2 assessed byin situmolecular characterization of satellite cells syncytia suggest a very strict correlation between BMP-2 expression and muscle regeneration capability. Summing up, the higher BMP-2 expression in osteoarthritic patients could explain the increased bone mineral density as well as decreased muscle atrophy in osteoarthrosic patients. In conclusion, our results suggest that the control of physiological BMP-2 balance between bone and muscle tissues may be considered as a potential pharmacological target in bone-muscle related pathology.

scholarly journals Myf5-Positive Satellite Cells Contribute to Pax7-Dependent Long-Term Maintenance of Adult Muscle Stem Cells

2013 ◽  
Vol 13 (6) ◽  
pp. 769
Author(s):  
Stefan Günther ◽  
Johnny Kim ◽  
Sawa Kostin ◽  
Christoph Lepper ◽  
Chen-Ming Fan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Satellite Cells ◽  
Muscle Stem Cells ◽  
Adult Muscle ◽  
Term Maintenance

scholarly journals Stem cells for skeletal muscle repair

2011 ◽  
Vol 366 (1575) ◽  
pp. 2297-2306 ◽  
Author(s):  
Jennifer L. Shadrach ◽  
Amy J. Wagers
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Muscle Disease ◽  
Muscle Fibres ◽  
Muscle Repair ◽  
Muscle Satellite Cells

Skeletal muscle is a highly specialized tissue composed of non-dividing, multi-nucleated muscle fibres that contract to generate force in a controlled and directed manner. Skeletal muscle is formed during embryogenesis from a subset of muscle precursor cells, which generate both differentiated muscle fibres and specialized muscle-forming stem cells known as satellite cells. Satellite cells remain associated with muscle fibres after birth and are responsible for muscle growth and repair throughout life. Failure in satellite cell function can lead to delayed, impaired or failed recovery after muscle injury, and such failures become increasingly prominent in cases of progressive muscle disease and in old age. Recent progress in the isolation of muscle satellite cells and elucidation of the cellular and molecular mediators controlling their activity indicate that these cells represent promising therapeutic targets. Such satellite cell-based therapies may involve either direct cell replacement or development of drugs that enhance endogenous muscle repair mechanisms. Here, we discuss recent breakthroughs in understanding both the cell intrinsic and extrinsic regulators that determine the formation and function of muscle satellite cells, as well as promising paths forward to realizing their full therapeutic potential.

scholarly journals Loss of myogenic potential and fusion capacity of muscle stem cells isolated from contractured muscle in children with cerebral palsy

2018 ◽  
Vol 315 (2) ◽  
pp. C247-C257 ◽  
Author(s):  
Andrea A. Domenighetti ◽  
Margie A. Mathewson ◽  
Rajeswari Pichika ◽  
Lydia A. Sibley ◽  
Leyna Zhao ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Cerebral Palsy ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Skeletal Muscles ◽  
Muscle Stem Cells ◽  
Myogenic Potential ◽  
Myotube Formation ◽  
The Brain

Cerebral palsy (CP) is the most common cause of pediatric neurodevelopmental and physical disability in the United States. It is defined as a group of motor disorders caused by a nonprogressive perinatal insult to the brain. Although the brain lesion is nonprogressive, there is a progressive, lifelong impact on skeletal muscles, which are shorter, spastic, and may develop debilitating contractures. Satellite cells are resident muscle stem cells that are indispensable for postnatal growth and regeneration of skeletal muscles. Here we measured the myogenic potential of satellite cells isolated from contractured muscles in children with CP. When compared with typically developing (TD) children, satellite cell-derived myoblasts from CP differentiated more slowly (slope: 0.013 (SD 0.013) CP vs. 0.091 (SD 0.024) TD over 24 h, P < 0.001) and fused less (fusion index: 21.3 (SD 8.6) CP vs. 81.3 (SD 7.7) TD after 48 h, P < 0.001) after exposure to low-serum conditions that stimulated myotube formation. This impairment was associated with downregulation of several markers important for myoblast fusion and myotube formation, including DNA methylation-dependent inhibition of promyogenic integrin-β 1D (ITGB1D) protein expression levels (−50% at 42 h), and ~25% loss of integrin-mediated focal adhesion kinase phosphorylation. The cytidine analog 5-Azacytidine (5-AZA), a demethylating agent, restored ITGB1D levels and promoted myogenesis in CP cultures. Our data demonstrate that muscle contractures in CP are associated with loss of satellite cell myogenic potential that is dependent on DNA methylation patterns affecting expression of genetic programs associated with muscle stem cell differentiation and muscle fiber formation.

scholarly journals In Vivo Study of Key Transcription Factors in Muscle Satellite Cells by CRISPR/Cas9/AAV9-sgRNA Mediated Genome Editing

2019 ◽  
Author(s):  
Liangqiang He ◽  
Yingzhe Ding ◽  
Yu Zhao ◽  
Karl K. So ◽  
Xianlu L. Peng ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Genome Editing ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Muscle Stem Cells ◽  
Muscle Satellite Cells ◽  
Regulatory Functions

ABSTRACTSkeletal muscle satellite cells (SCs) are adult muscle stem cells responsible for injury induced muscle regeneration. Despite advances in the knowledge of molecular mechanisms regulating SC lineage progression, our understanding of key transcription factors (TFs) and their regulatory functions in SCs in particularly the quiescent and early activation stages remains incomplete due to the lack of efficient method to screen and investigate the stage-specific key TFs. In this study, we succeeded in defining a distinct list of key TFs in early stages of SC fate transition using the paradigm of super enhancers (SEs). Particularly, leveraging the Cre-dependent Cas9 knockin mice and AAV9 mediated sgRNAs delivery, we generated a facile muscle specific genome editing system which allows gene depletion in SCs in vivo. Using MyoD locus as a proof of concept, we demonstrated that this CRISPR/Cas9/AAV9-sgRNA system can efficiently introduce mutagenesis at target locus and recapture the phenotypes reported in knockout mice. Further application of the system on key TFs, Myc, Bcl6 and Pknox2, revealed their distinct functions in the early stage of SC activation and damage induced muscle regeneration. Altogether our findings have proven the CRISPR/Cas9/AAV9-sgRNA system as a robust way for in vivo genome editing and elucidation of key factors governing SC activities.

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