scholarly journals Abundant Synthesis of Netrin-1 in Satellite Cell-Derived Myoblasts Isolated from EDL Rather Than Soleus Muscle Regulates Fast-Type Myotube Formation

2021 ◽  
Vol 22 (9) ◽  
pp. 4499
Author(s):  
Takahiro Suzuki ◽  
Aika Mori ◽  
Takahiro Maeno ◽  
Rio Arimatsu ◽  
Emi Ichimura ◽  
...  
Keyword(s):  
Satellite Cell ◽  
Soleus Muscle ◽  
Satellite Cells ◽  
Myogenic Differentiation ◽  
Membrane Receptors ◽  
Myogenic Stem Cells ◽  
Slow Fiber ◽  
Fast Fiber ◽  
Fast Twitch ◽  
Myofiber Type

Resident myogenic stem cells (satellite cells) are attracting attention for their novel roles in myofiber type regulation. In the myogenic differentiation phase, satellite cells from soleus muscle (slow fiber-abundant) synthesize and secrete higher levels of semaphorin 3A (Sema3A, a multifunctional modulator) than those derived from extensor digitorum longus (EDL; fast fiber-abundant), suggesting the role of Sema3A in forming slow-twitch myofibers. However, the regulatory mechanisms underlying fast-twitch myotube commitment remain unclear. Herein, we focused on netrin family members (netrin-1, -3, and -4) that compete with Sema3A in neurogenesis and osteogenesis. We examined whether netrins affect fast-twitch myotube generation by evaluating their expression in primary satellite cell cultures. Initially, netrins are upregulated during myogenic differentiation. Next, we compared the expression levels of netrins and their cell membrane receptors between soleus- and EDL-derived satellite cells; only netrin-1 showed higher expression in EDL-derived satellite cells than in soleus-derived satellite cells. We also performed netrin-1 knockdown experiments and additional experiments with recombinant netrin-1 in differentiated satellite cell-derived myoblasts. Netrin-1 knockdown in myoblasts substantially reduced fast-type myosin heavy chain (MyHC) expression; exogenous netrin-1 upregulated fast-type MyHC in satellite cells. Thus, netrin-1 synthesized in EDL-derived satellite cells may promote myofiber type commitment of fast muscles.

scholarly journals Metformin Delays Satellite Cell Activation and Maintains Quiescence

2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Theodora Pavlidou ◽  
Milica Marinkovic ◽  
Marco Rosina ◽  
Claudia Fuoco ◽  
Simone Vumbaca ◽  
...  
Keyword(s):  
Satellite Cell ◽  
Muscle Tissue ◽  
Satellite Cells ◽  
Cell Activation ◽  
Myogenic Differentiation ◽  
Metabolic State ◽  
Cell Pool ◽  
Age Related ◽  
Satellite Cell Activation

The regeneration of the muscle tissue relies on the capacity of the satellite stem cell (SC) population to exit quiescence, divide asymmetrically, proliferate, and differentiate. In age-related muscle atrophy (sarcopenia) and several dystrophies, regeneration cannot compensate for the loss of muscle tissue. These disorders are associated with the depletion of the satellite cell pool or with the loss of satellite cell functionality. Recently, the establishment and maintenance of quiescence in satellite cells have been linked to their metabolic state. In this work, we aimed to modulate metabolism in order to preserve the satellite cell pool. We made use of metformin, a calorie restriction mimicking drug, to ask whether metformin has an effect on quiescence, proliferation, and differentiation of satellite cells. We report that satellite cells, when treated with metformin in vitro, ex vivo, or in vivo, delay activation, Pax7 downregulation, and terminal myogenic differentiation. We correlate the metformin-induced delay in satellite cell activation with the inhibition of the ribosome protein RPS6, one of the downstream effectors of the mTOR pathway. Moreover, in vivo administration of metformin induces a belated regeneration of cardiotoxin- (CTX-) damaged skeletal muscle. Interestingly, satellite cells treated with metformin immediately after isolation are smaller in size and exhibit reduced pyronin Y levels, which suggests that metformin-treated satellite cells are transcriptionally less active. Thus, our study suggests that metformin delays satellite cell activation and differentiation by favoring a quiescent, low metabolic state.

Growth factor regulation of neural chemorepellent Sema3A expression in satellite cell cultures

2011 ◽  
Vol 301 (5) ◽  
pp. C1270-C1279 ◽  
Author(s):  
Mai-Khoi Q. Do ◽  
Yusuke Sato ◽  
Naomi Shimizu ◽  
Takahiro Suzuki ◽  
Jun-ichi Shono ◽  
...  
Keyword(s):  
Growth Factor ◽  
Satellite Cell ◽  
Cell Cultures ◽  
Muscle Fiber ◽  
Satellite Cells ◽  
Transforming Growth Factor ◽  
Maximum Effect ◽  
Initial Report ◽  
Myogenic Stem Cells

Successful regeneration and remodeling of the intramuscular motoneuron network and neuromuscular connections are critical for restoring skeletal muscle function and physiological properties. The regulatory signals of such coordination remain unclear, although axon-guidance molecules may be involved. Recently, satellite cells, resident myogenic stem cells positioned beneath the basal lamina and at high density at the myoneural junction regions of mature fibers, were shown to upregulate a secreted neural chemorepellent semaphorin 3A (Sema3A) in response to in vivo muscle-crush injury. The initial report on that expression centered on the observation that hepatocyte growth factor (HGF), an essential cue in muscle fiber growth and regeneration, remarkably upregulates Sema3A expression in early differentiated satellite cells in vitro [Tatsumi et al., Am J Physiol Cell Physiol 297: C238–C252, 2009]. Here, we address regulatory effects of basic fibroblast growth factor (FGF2) and transforming growth factor (TGF)-βs on Sema3A expression in satellite cell cultures. When treated with FGF2, Sema3A message and protein were upregulated as revealed by reverse transcription-polymerase chain reaction and immunochemical studies. Sema3A upregulation by FGF2 was dose dependent with a maximum (8- to 1-fold relative to the control) at 2.5 ng/ml (150 pM) and occurred exclusively at the early differentiation stage. The response was highly comparable in dose response and timing to effects of HGF treatment, without any additive or synergistic effect from treatment with a combination of both potent upregulators. In contrast, TGF-β2 and -β3 potently decreased basal Sema3A expression; the maximum effect was at very low concentrations (40 and 8 pM, respectively) and completely cancelled the activities of FGF2 and HGF to upregulate Sema3A. These results therefore encourage the prospect that a time-coordinated increase in HGF, FGF2, and TGF-β ligands and their receptors promotes a programmed strategy for Sema3A expression that guarantees successful intramuscular motor reinnervation by delaying sprouting and reattachment of motoneuron terminals onto damaged muscle fibers early in regeneration pending restoration of muscle fiber contractile integrity.

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.

Intrinsic, extrinsic and environmental regulation of muscle satellite cell motility

2011 ◽  
Author(s):  
◽  
Ashley Lynn Siegal
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cell Motility ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Tibialis Anterior Muscle ◽  
Repulsive Interaction ◽  
Myogenic Stem Cells ◽  
Hepatocyte Growth

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Skeletal muscle repair and regeneration requires the activity of satellite cells, a population of myogenic stem cells. Previously, little data existed on the motility of satellite cells a critical component to tissue repair. Using timelapse videomicroscopy to assess satellite cell motility on the surface of single living myofibers, we have identified a requirement for the laminin-binding integrin a7b1 in satellite cell motility, as well as a role for hepatocyte growth factor in promoting directional persistence. We also observed more persistent long-term contact, potential cell-cell attractive and repulsive interaction, and migration between host myofibers. We found that satellite cells express multiple members of each of the four major families of guidance molecules. Satellite cell migration in vivo may be more extensive than currently thought, and could be regulated by combinations of signals including adhesive haptotaxis, soluble factors, and guidance cues. CXCL12/SDF-1 and hepatocyte growth factor/scatter factor (HGF) are included in these released factors satellite cell displacement and velocity and chemotaxis were quantified. Purified HGF and SDF-1a were injected into the Tibialis Anterior muscle (TA) to test the sufficiency of these factors for satellite cell movement in vivo. A better understanding of how satellite cells actually respond to an injury in a healthy muscle and if they are mobilized and motile from a distance will be critical to knowing if they can be induced to move through damaged or diseased muscle tissue.

scholarly journals High concentrations of HGF inhibit skeletal muscle satellite cell proliferation in vitro by inducing expression of myostatin: a possible mechanism for reestablishing satellite cell quiescence in vivo

2010 ◽  
Vol 298 (3) ◽  
pp. C465-C476 ◽  
Author(s):  
Michiko Yamada ◽  
Ryuichi Tatsumi ◽  
Keitaro Yamanouchi ◽  
Tohru Hosoyama ◽  
Sei-ichi Shiratsuchi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Time Lag ◽  
Dependent Manner ◽  
Western Blots ◽  
Myogenic Stem Cells ◽  
Cell Quiescence ◽  
High Concentrations

Skeletal muscle regeneration and work-induced hypertrophy rely on molecular events responsible for activation and quiescence of resident myogenic stem cells, satellite cells. Recent studies demonstrated that hepatocyte growth factor (HGF) triggers activation and entry into the cell cycle in response to mechanical perturbation, and that subsequent expression of myostatin may signal a return to cell quiescence. However, mechanisms responsible for coordinating expression of myostatin after an appropriate time lag following activation and proliferation are not clear. Here we address the possible role of HGF in quiescence through its concentration-dependent negative-feedback mechanism following satellite cell activation and proliferation. When activated/proliferating satellite cell cultures were treated for 24 h beginning 48-h postplating with 10–500 ng/ml HGF, the percentage of bromodeoxyuridine-incorporating cells decreased down to a baseline level comparable to 24-h control cultures in a HGF dose-dependent manner. The high level HGF treatment did not impair the cell viability and differentiation levels, and cells could be reactivated by lowering HGF concentrations to 2.5 ng/ml, a concentration that has been shown to optimally stimulate activation of satellite cells in culture. Coaddition of antimyostatin neutralizing antibody could prevent deactivation and abolish upregulation of cyclin-dependent kinase (Cdk) inhibitor p21. Myostatin mRNA expression was upregulated with high concentrations of HGF, as demonstrated by RT-PCR, and enhanced myostatin protein expression and secretion were revealed by Western blots of the cell lysates and conditioned media. These results indicate that HGF could induce satellite cell quiescence by stimulating myostatin expression. The HGF concentration required (over 10–50 ng/ml), however, is much higher than that for activation, which is initiated by rapid release of HGF from its extracellular association. Considering that HGF is produced by satellite cells and spleen and liver cells in response to muscle damage, local concentrations of HGF bathing satellite cells may reach a threshold sufficient to induce myostatin expression. This time lag may delay action of the quiescence signaling program in proliferating satellite cells during initial phases of muscle regeneration followed by induction of quiescence in a subset of cells during later phases.

scholarly journals An Overview About the Biology of Skeletal Muscle Satellite Cells

2019 ◽  
Vol 20 (1) ◽  
pp. 24-37 ◽  
Author(s):  
Laura Forcina ◽  
Carmen Miano ◽  
Laura Pelosi ◽  
Antonio Musarò
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Satellite Cell ◽  
Muscle Tissue ◽  
Satellite Cells ◽  
Cell Biology ◽  
Regulatory Networks ◽  
Myogenic Differentiation ◽  
Cell Activity ◽  
Quiescent State

The peculiar ability of skeletal muscle tissue to operate adaptive changes during post-natal development and adulthood has been associated with the existence of adult somatic stem cells. Satellite cells, occupying an exclusive niche within the adult muscle tissue, are considered bona fide stem cells with both stem-like properties and myogenic activities. Indeed, satellite cells retain the capability to both maintain the quiescence in uninjured muscles and to be promptly activated in response to growth or regenerative signals, re-engaging the cell cycle. Activated cells can undergo myogenic differentiation or self-renewal moving back to the quiescent state. Satellite cells behavior and their fate decision are finely controlled by mechanisms involving both cell-autonomous and external stimuli. Alterations in these regulatory networks profoundly affect muscle homeostasis and the dynamic response to tissue damage, contributing to the decline of skeletal muscle that occurs under physio-pathologic conditions. Although the clear myogenic activity of satellite cells has been described and their pivotal role in muscle growth and regeneration has been reported, a comprehensive picture of inter-related mechanisms guiding muscle stem cell activity has still to be defined. Here, we reviewed the main regulatory networks determining satellite cell behavior. In particular, we focused on genetic and epigenetic mechanisms underlining satellite cell maintenance and commitment. Besides intrinsic regulations, we reported current evidences about the influence of environmental stimuli, derived from other cell populations within muscle tissue, on satellite cell biology.

scholarly journals Satellite cells and their regulation in livestock

2020 ◽  
Vol 98 (5) ◽  
Author(s):  
Madison L Gonzalez ◽  
Nicolas I Busse ◽  
Christy M Waits ◽  
Sally E Johnson
Keyword(s):  
Growth Factor ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Intracellular Signaling ◽  
Transforming Growth Factor ◽  
Myogenic Differentiation ◽  
Cell Activity ◽  
Large Animal ◽  
Quiescent State ◽  
Proliferation And Differentiation

Abstract Satellite cells are the myogenic stem and progenitor population found in skeletal muscle. These cells typically reside in a quiescent state until called upon to support repair, regeneration, or muscle growth. The activities of satellite cells are orchestrated by systemic hormones, autocrine and paracrine growth factors, and the composition of the basal lamina of the muscle fiber. Several key intracellular signaling events are initiated in response to changes in the local environment causing exit from quiescence, proliferation, and differentiation. Signals emanating from Notch, wingless-type mouse mammary tumor virus integration site family members, and transforming growth factor-β proteins mediate the reversible exit from growth 0 phase while those initiated by members of the fibroblast growth factor and insulin-like growth factor families direct proliferation and differentiation. Many of these pathways impinge upon the myogenic regulatory factors (MRF), myogenic factor 5, myogenic differentiation factor D, myogenin and MRF4, and the lineage determinate, Paired box 7, to alter transcription and subsequent satellite cell decisions. In the recent past, insight into mouse transgenic models has led to a firm understanding of regulatory events that control satellite cell metabolism and myogenesis. Many of these niche-regulated functions offer subtle differences from their counterparts in livestock pointing to the existence of species-specific controls. The purpose of this review is to examine the mechanisms that mediate large animal satellite cell activity and their relationship to those present in rodents.

Skeletal Muscle Regeneration: MSC versus Satellite Cells

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P86-P86
Author(s):  
Jens Stern-Straeter ◽  
Juritz Stephanie ◽  
Gregor Bran ◽  
Frank Riedel ◽  
Haneen Sadick ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Satellite Cell ◽  
Cell Cultures ◽  
Muscle Tissue ◽  
Satellite Cells ◽  
Myogenic Differentiation ◽  
Culture Conditions ◽  
Muscle Biopsies

Problem Differentiating stem cells into the myogenic linage in order to create functional muscle tissue is a challenging endeavour. In this work, adipose-derived mesenchymal stem cells (MSC) and satellite cells derived from muscle biopsies were compared regarding proliferation and myogenic differentiation potential under standardized cell culture conditions. This data was obtained in order to discover the most promising type of stem cell for regeneration of muscle tissue and to determine the optimal culture conditions for later clinical use. Methods Human MSC were isolated from adipose tissue, and primary human skeletal myoblasts were extracted from muscle biopsies by enzymatic digestion. Proliferation was analysed using the AlamarBlue® assay. Gene expression of marker genes – such as Myogenin, Myo D, Myf 5 and MHC – were analysed by RT-PCR. Immunostainings against desmin and sarcomeric-actin were performed as differentiation markers. Results MSC cell cultures showed a greater proliferation rate compared with satellite cell cultures. In both stem cell cultures, myogenic differentiation/heritage could be verified by immunostainings against the muscle-specific marker desmin. Gene expression and protein analysis revealed a more stable differentiation of human satellite cell cultures. Conclusion Characterization of both human MSC cultures and satellite cell cultures – and thereby an understanding of myogenesis – might lead to their clinical usage in skeletal muscle tissue engineering. The results in this study appear to indicate that human satellite cell cultures have a more stable differentiation under in vitro conditions and that they might offer a greater potential for skeletal muscle tissue engineering purposes. Significance Our study contributes to the understanding of myogenic differentiation of MSC and satellite cells and helps to improve culture systems for later clinical utilization.

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 The Skeletal Muscle Satellite Cell

2011 ◽  
Vol 59 (12) ◽  
pp. 1041-1059 ◽  
Author(s):  
Zipora Yablonka-Reuveni
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
50Th Anniversary ◽  
Basement Membranes ◽  
Whole Body ◽  
Muscle Satellite Cell ◽  
Cell Based Therapy ◽  
Myogenic Stem Cells ◽  
Skeletal Muscle Satellite Cell

The skeletal muscle satellite cell was first described and named based on its anatomic location between the myofiber plasma and basement membranes. In 1961, two independent studies by Alexander Mauro and Bernard Katz provided the first electron microscopic descriptions of satellite cells in frog and rat muscles. These cells were soon detected in other vertebrates and acquired candidacy as the source of myogenic cells needed for myofiber growth and repair throughout life. Cultures of isolated myofibers and, subsequently, transplantation of single myofibers demonstrated that satellite cells were myogenic progenitors. More recently, satellite cells were redefined as myogenic stem cells given their ability to self-renew in addition to producing differentiated progeny. Identification of distinctively expressed molecular markers, in particular Pax7, has facilitated detection of satellite cells using light microscopy. Notwithstanding the remarkable progress made since the discovery of satellite cells, researchers have looked for alternative cells with myogenic capacity that can potentially be used for whole body cell-based therapy of skeletal muscle. Yet, new studies show that inducible ablation of satellite cells in adult muscle impairs myofiber regeneration. Thus, on the 50th anniversary since its discovery, the satellite cell’s indispensable role in muscle repair has been reaffirmed.

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