scholarly journals Entry of muscle satellite cells into the cell cycle requires sphingolipid signaling

2006 ◽  
Vol 174 (2) ◽  
pp. 245-253 ◽  
Author(s):  
Yosuke Nagata ◽  
Terence A. Partridge ◽  
Ryoichi Matsuda ◽  
Peter S. Zammit
Keyword(s):  
Cell Cycle ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Adult Stem Cell ◽  
Adult Skeletal Muscle ◽  
Crucial Step ◽  
Sphingosine 1 Phosphate ◽  
Mitogenic Signal

Adult skeletal muscle is able to repeatedly regenerate because of the presence of satellite cells, a population of stem cells resident beneath the basal lamina that surrounds each myofiber. Little is known, however, of the signaling pathways involved in the activation of satellite cells from quiescence to proliferation, a crucial step in muscle regeneration. We show that sphingosine-1-phosphate induces satellite cells to enter the cell cycle. Indeed, inhibiting the sphingolipid-signaling cascade that generates sphingosine-1-phosphate significantly reduces the number of satellite cells able to proliferate in response to mitogen stimulation in vitro and perturbs muscle regeneration in vivo. In addition, metabolism of sphingomyelin located in the inner leaflet of the plasma membrane is probably the main source of sphingosine-1-phosphate used to mediate the mitogenic signal. Together, our observations show that sphingolipid signaling is involved in the induction of proliferation in an adult stem cell and a key component of muscle regeneration.

scholarly journals Intact satellite cells lead to remarkable protection against Smn gene defect in differentiated skeletal muscle

2003 ◽  
Vol 161 (3) ◽  
pp. 571-582 ◽  
Author(s):  
Sophie Nicole ◽  
Benedicte Desforges ◽  
Gaelle Millet ◽  
Jeanne Lesbordes ◽  
Carmen Cifuentes-Diaz ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Motor Performance ◽  
Muscular Atrophy ◽  
Early Death ◽  
Mutant Mice ◽  
Mild Phenotype

Deletion of murine Smn exon 7, the most frequent mutation found in spinal muscular atrophy, has been directed to either both satellite cells, the muscle progenitor cells and fused myotubes, or fused myotubes only. When satellite cells were mutated, mutant mice develop severe myopathic process, progressive motor paralysis, and early death at 1 mo of age (severe mutant). Impaired muscle regeneration of severe mutants correlated with defect of myogenic precursor cells both in vitro and in vivo. In contrast, when satellite cells remained intact, mutant mice develop similar myopathic process but exhibit mild phenotype with median survival of 8 mo and motor performance similar to that of controls (mild mutant). High proportion of regenerating myofibers expressing SMN was observed in mild mutants compensating for progressive loss of mature myofibers within the first 6 mo of age. Then, in spite of normal contractile properties of myofibers, mild mutants develop reduction of muscle force and mass. Progressive decline of muscle regeneration process was no more able to counterbalance muscle degeneration leading to dramatic loss of myofibers. These data indicate that intact satellite cells remarkably improve the survival and motor performance of mutant mice suffering from chronic myopathy, and suggest a limited potential of satellite cells to regenerate skeletal muscle.

scholarly journals In Vivo Activation of STAT3 Signaling in Satellite Cells and Myofibers in Regenerating Rat Skeletal Muscles

2002 ◽  
Vol 50 (12) ◽  
pp. 1579-1589 ◽  
Author(s):  
Katsuya Kami ◽  
Emiko Senba
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Intracellular Signaling ◽  
Skeletal Muscles ◽  
Early Stage ◽  
Skeletal Muscle Regeneration ◽  
Stat3 Signaling

Although growth factors and cytokines play critical roles in skeletal muscle regeneration, intracellular signaling molecules that are activated by these factors in regenerating muscles have been not elucidated. Several lines of evidence suggest that leukemia inhibitory factor (LIF) is an important cytokine for the proliferation and survival of myoblasts in vitro and acceleration of skeletal muscle regeneration. To elucidate the role of LIF signaling in regenerative responses of skeletal muscles, we examined the spatial and temporal activation patterns of an LIF-associated signaling molecule, the signal transducer and activator transcription 3 (STAT3) proteins in regenerating rat skeletal muscles induced by crush injury. At the early stage of regeneration, activated STAT3 proteins were first detected in the nuclei of activated satellite cells and then continued to be activated in proliferating myoblasts expressing both PCNA and MyoD proteins. When muscle regeneration progressed, STAT3 signaling was no longer activated in differentiated myoblasts and myotubes. In addition, activation of STAT3 was also detected in myonuclei within intact sarcolemmas of surviving myofibers that did not show signs of necrosis. These findings suggest that activation of STAT3 signaling is an important molecular event that induces the successful regeneration of injured skeletal muscles.

Dynamic distribution and formation of a para-sarcomeric banding pattern of prosomes during myogenic differentiation of satellite cells in vitro

1999 ◽  
Vol 112 (7) ◽  
pp. 989-1001 ◽  
Author(s):  
J. Foucrier ◽  
M.C. Grand ◽  
F. De Conto ◽  
Y. Bassaglia ◽  
G. Geraud ◽  
...  
Keyword(s):  
Satellite Cells ◽  
Banding Pattern ◽  
Myogenic Differentiation ◽  
In Vitro Differentiation ◽  
Adult Skeletal Muscle ◽  
Myogenic Stem Cells ◽  
Alpha Actin ◽  
Type Intermediate

Myogenesis proceeds by fusion of proliferating myoblasts into myotubes under the control of various transcription factors. In adult skeletal muscle, myogenic stem cells are represented by the satellite cells which can be cultured and differentiate in vitro. This system was used to investigate the subcellular distribution of a particular type of prosomes at different steps of the myogenic process. Prosomes constitute the MCP core of the 26S proteasomes but were first observed as subcomplexes of the untranslated mRNPs; recently, their RNase activity was discovered. A monoclonal antibody raised against the p27K subunit showed that the p27K subunit-specific prosomes move transiently into the nucleus prior to the onset of myoblast fusion into myotubes; this represents possibly one of the first signs of myoblast switching into the differentiation pathway. Prior to fusion, the prosomes containing the p27K subunit return to the cytoplasm, where they align with the gradually formed lengthwise-running desmin-type intermediate filaments and the microfilaments, co-localizing finally with the actin bundles. The prosomes progressively form discontinuous punctate structures which eventually develop a pseudo-sarcomeric banding pattern. In myotubes just formed in vitro, the formation of this pattern seems to preceed that produced by the muscle-specific sarcomeric (alpha)-actin. Interestingly, this pattern of prosomes of myotubes in terminal in vitro differentiation was very similar to that of prosomes observed in vivo in foetal and adult muscle. These observations are discussed in relation to molecular myogenesis and prosome/proteasome function.

Tristetraprolin and LPS-inducible CXC chemokine are rapidly induced in presumptive satellite cells in response to skeletal muscle injury

2002 ◽  
Vol 115 (13) ◽  
pp. 2701-2712 ◽  
Author(s):  
Chetana Sachidanandan ◽  
Ramkumar Sambasivan ◽  
Jyotsna Dhawan
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Cell Biology ◽  
Muscle Injury ◽  
Rna Binding ◽  
C2c12 Myoblasts ◽  
Adult Skeletal Muscle ◽  
Cxc Chemokine

Myogenic precursor cells known as satellite cells persist in adult skeletal muscle and are responsible for its ability to regenerate after injury. Quiescent satellite cells are activated by signals emanating from damaged muscle. Here we describe the rapid activation of two genes in response to muscle injury; these transcripts encode LPS-inducible CXC chemokine (LIX), a neutrophil chemoattractant, and Tristetraprolin (TTP), an RNA-binding protein implicated in the regulation of cytokine expression. Using a synchronized cell culture model we show that C2C12 myoblasts arrested in G0 exhibit some molecular attributes of satellite cells in vivo: suppression of MyoD and Myf5 expression during G0 and their reactivation in G1. Synchronization also revealed cell cycle dependent expression of CD34, M-cadherin, HGF and PEA3, genes implicated in satellite cell biology. To identify other genes induced in synchronized C2C12 myoblasts we used differential display PCR and isolated LIX and TTP cDNAs. Both LIX and TTP mRNAs are short-lived, encode molecules implicated in inflammation and are transiently induced during growth activation in vitro. Further, LIX and TTP are rapidly induced in response to muscle damage in vivo. TTP expression precedes that of MyoD and is detected 30 minutes after injury. The spatial distribution of LIX and TTP transcripts in injured muscle suggests expression by satellite cells. Our studies suggest that in addition to generating new cells for repair, activated satellite cells may be a source of signaling molecules involved in tissue remodeling during regeneration.

scholarly journals S1P2 receptor promotes mouse skeletal muscle regeneration

2012 ◽  
Vol 113 (5) ◽  
pp. 707-713 ◽  
Author(s):  
Elena Germinario ◽  
Samantha Peron ◽  
Luana Toniolo ◽  
Romeo Betto ◽  
Francesca Cencetti ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Muscle Growth ◽  
Skeletal Muscle Regeneration ◽  
Null Mouse ◽  
Sphingosine 1 Phosphate ◽  
Functional Inactivation

Sphingosine 1-phosphate is a bioactive lipid that modulates skeletal muscle growth through its interaction with specific receptors localized in the cell membrane of muscle fibers and satellite cells. This study analyzes the role of S1P2 receptor during in vivo regeneration of soleus muscle in two models of S1P2 deficiency: the S1P2-null mouse and wild-type mice systemically treated with the S1P2 receptor antagonist JTE-013. To stimulate regeneration, muscle degeneration was induced by injecting into soleus muscle the myotoxic drug notexin. Both ablation of S1P2 receptor and its functional inactivation delayed regeneration of soleus muscle. The exogenous supplementation of S1P or its removal, by a specific antibody, two conditions known to stimulate or inhibit, respectively, soleus muscle regeneration, were without effects when the S1P2 receptor was absent or inactive. The delayed regeneration was associated with a lower level of myogenin, a muscle differentiation marker, and reduced phosphorylation of Akt, a key marker of muscle growth. Consistently, silencing of S1P2 receptor abrogated the pro-myogenic action of S1P in satellite cells, paralleled by low levels of the myogenic transcription factor myogenin. The study indicates that S1P2 receptor plays a key role in the early phases of muscle regeneration by sustaining differentiation and growth of new-forming myofibers.

M-cadherin transcription in satellite cells from normal and denervated muscle

2004 ◽  
Vol 286 (3) ◽  
pp. C708-C712 ◽  
Author(s):  
Annette Maier ◽  
Antje Bornemann
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Satellite Cells ◽  
Galactosidase Activity ◽  
Rt Pcr ◽  
Denervated Muscle ◽  
Rat Muscle ◽  
Hindlimb Muscles

Satellite cells (SC) in adult muscle are quiescent in the G0 phase of the cell cycle. In the present study we determined whether SC after denervation upregulate M-cadherin, an adhesion molecule that is upregulated with differentiation and fusion. We also monitored primary cultures of SC from denervated muscle for expression of the transcription factors of the MyoD family to determine whether SC from denervated muscle can be activated in vitro. Hindlimb muscles of rats were denervated under anesthesia, and rats were killed after 2-28 days. The SC of the denervated limbs were pooled and either assessed for M-cadherin mRNA by using real-time RT-PCR or cultured in vitro. The cultures were processed for RT-PCR or immunofluorescence for expression of the transcription factors of the MyoD family. Hindlimb muscles of M-cadherin knockout mice were denervated under anesthesia, mice were killed after 2-28 days, and cells were stained for β-galactosidase activity by X-gal histochemistry. In vitro, primary SC cultures from rat muscle denervated for 2-28 days expressed transcripts of myf5, MyoD, myogenin, and MRF4 as SC from normal innervated muscle. In vivo, M-cadherin transcription was not upregulated in SC from denervated rat muscle when compared with normal muscle. Moreover, β-galactosidase activity was not detected in denervated mouse muscle. The finding that SC do not upregulate M-cadherin after denervation supports the notion that they remain in the G0 phase of the cell cycle in vivo. However, the cells retain the capacity to pass through the proliferative and differentiative program when robustly stimulated to do so in vitro.

scholarly journals A role for the ETS domain transcription factor PEA3 in myogenic differentiation.

1997 ◽  
Vol 17 (9) ◽  
pp. 5550-5558 ◽  
Author(s):  
J M Taylor ◽  
E E Dupont-Versteegden ◽  
J D Davies ◽  
J A Hassell ◽  
J D Houlé ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Satellite Cells ◽  
Cell Function ◽  
Myogenic Differentiation ◽  
Muscle Degeneration ◽  
Adult Skeletal Muscle ◽  
Myogenic Stem Cells ◽  
Important Regulator

Activation of adult myoblasts called satellite cells during muscle degeneration is an important aspect of muscle regeneration. Satellite cells are believed to be the only myogenic stem cells in adult skeletal muscle and the source of regenerating muscle fibers. Upon activation, satellite cells proliferate, migrate to the site of degeneration, and become competent to fuse and differentiate. We show here that the transcription factor polyomavirus enhancer activator 3 (PEA3) is expressed in adult myoblasts in vitro when they are proliferative and during the early stages of differentiation. Overexpression of PEA3 accelerates differentiation, whereas blocking of PEA3 function delays myoblast fusion. PEA3 activates gene expression following binding to the ets motif most efficiently in conjunction with the transcription factor myocyte enhancer factor 2 (MEF2). In vivo, PEA3 is expressed in satellite cells only after muscle degeneration. Taken together, these results suggest that PEA3 is an important regulator of activated satellite cell function.

scholarly journals Reduced Differentiation Potential of Primary MyoD−/− Myogenic Cells Derived from Adult Skeletal Muscle

1999 ◽  
Vol 144 (4) ◽  
pp. 631-643 ◽  
Author(s):  
Luc A. Sabourin ◽  
Adele Girgis-Gabardo ◽  
Patrick Seale ◽  
Atsushi Asakura ◽  
Michael A. Rudnicki
Keyword(s):  
Satellite Cells ◽  
Northern Analysis ◽  
Intermediate Filament Protein ◽  
Wild Type ◽  
Differentiation Potential ◽  
Myogenic Cells ◽  
Adult Skeletal Muscle ◽  
Myogenic Precursor

To gain insight into the regeneration deficit of MyoD−/− muscle, we investigated the growth and differentiation of cultured MyoD−/− myogenic cells. Primary MyoD−/− myogenic cells exhibited a stellate morphology distinct from the compact morphology of wild-type myoblasts, and expressed c-met, a receptor tyrosine kinase expressed in satellite cells. However, MyoD−/− myogenic cells did not express desmin, an intermediate filament protein typically expressed in cultured myoblasts in vitro and myogenic precursor cells in vivo. Northern analysis indicated that proliferating MyoD−/− myogenic cells expressed fourfold higher levels of Myf-5 and sixfold higher levels of PEA3, an ETS-domain transcription factor expressed in newly activated satellite cells. Under conditions that normally induce differentiation, MyoD−/− cells continued to proliferate and with delayed kinetics yielded reduced numbers of predominantly mononuclear myocytes. Northern analysis revealed delayed induction of myogenin, MRF4, and other differentiation-specific markers although p21 was upregulated normally. Expression of M-cadherin mRNA was severely decreased whereas expression of IGF-1 was markedly increased in MyoD−/− myogenic cells. Mixing of lacZ-labeled MyoD−/− cells and wild-type myoblasts revealed a strict autonomy in differentiation potential. Transfection of a MyoD-expression cassette restored cytomorphology and rescued the differentiation deficit. We interpret these data to suggest that MyoD−/− myogenic cells represent an intermediate stage between a quiescent satellite cell and a myogenic precursor cell.

scholarly journals c-Abl Kinase Is Required for Satellite Cell Function Through Pax7 Regulation

2021 ◽  
Vol 9 ◽  
Author(s):  
Fabián Montecino ◽  
Natalia González ◽  
Natasha Blanco ◽  
Manuel J. Ramírez ◽  
Adrián González-Martín ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Muscle Regeneration ◽  
Cell Function ◽  
Mapk Pathway ◽  
Skeletal Muscle Regeneration ◽  
Acute Injury ◽  
Loss Of Function ◽  
Adult Skeletal Muscle

Satellite cells (SCs) are tissue-specific stem cells responsible for adult skeletal muscle regeneration and maintenance. SCs function is critically dependent on two families of transcription factors: the paired box (Pax) involved in specification and maintenance and the Muscle Regulatory Factors (MRFs), which orchestrate myogenic commitment and differentiation. In turn, signaling events triggered by extrinsic and intrinsic stimuli control their function via post-translational modifications, including ubiquitination and phosphorylation. In this context, the Abelson non-receptor tyrosine kinase (c-Abl) mediates the activation of the p38 α/β MAPK pathway, promoting myogenesis. c-Abl also regulates the activity of the transcription factor MyoD during DNA-damage stress response, pausing differentiation. However, it is not clear if c-Abl modulates other key transcription factors controlling SC function. This work aims to determine the role of c-Abl in SCs myogenic capacity via loss of function approaches in vitro and in vivo. Here we show that c-Abl inhibition or deletion results in a down-regulation of Pax7 mRNA and protein levels, accompanied by decreased Pax7 transcriptional activity, without a significant effect on MRF expression. Additionally, we provide data indicating that Pax7 is directly phosphorylated by c-Abl. Finally, SC-specific c-Abl ablation impairs muscle regeneration upon acute injury. Our results indicate that c-Abl regulates myogenic progression in activated SCs by controlling Pax7 function and expression.

scholarly journals A requirement of Polo-like kinase 1 in murine embryonic myogenesis and adult muscle regeneration

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Zhihao Jia ◽  
Yaohui Nie ◽  
Feng Yue ◽  
Yifan Kong ◽  
Lijie Gu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Muscle Regeneration ◽  
Muscle Development ◽  
Cell Cycle Regulators ◽  
Adult Muscle ◽  
M Phase ◽  
Postnatal Myogenesis ◽  
Cycle Regulation

Muscle development and regeneration require delicate cell cycle regulation of embryonic myoblasts and adult muscle satellite cells (MuSCs). Through analysis of the Polo-like kinase (Plk) family cell-cycle regulators in mice, we show that Plk1’s expression closely mirrors myoblast dynamics during embryonic and postnatal myogenesis. Cell-specific deletion of Plk1 in embryonic myoblasts leads to depletion of myoblasts, developmental failure and prenatal lethality. Postnatal deletion of Plk1 in MuSCs does not perturb their quiescence but depletes activated MuSCs as they enter the cell cycle, leading to regenerative failure. The Plk1-null MuSCs are arrested at the M-phase, accumulate DNA damage, and apoptose. Mechanistically, Plk1 deletion upregulates p53, and inhibition of p53 promotes survival of the Plk1-null myoblasts. Pharmacological inhibition of Plk1 similarly inhibits proliferation but promotes differentiation of myoblasts in vitro, and blocks muscle regeneration in vivo. These results reveal for the first time an indispensable role of Plk1 in developmental and regenerative myogenesis.

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