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.

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 The transcription factor NF-Y participates to stem cell fate decision and regeneration in adult skeletal muscle

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Giovanna Rigillo ◽  
Valentina Basile ◽  
Silvia Belluti ◽  
Mirko Ronzio ◽  
Elisabetta Sauta ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Transcription Factor ◽  
Stem Cell ◽  
Satellite Cells ◽  
Cell Biology ◽  
Myogenic Differentiation ◽  
Stem Cell Population ◽  
Adult Skeletal Muscle ◽  
Muscle Stem Cells

AbstractThe transcription factor NF-Y promotes cell proliferation and its activity often declines during differentiation through the regulation of NF-YA, the DNA binding subunit of the complex. In stem cell compartments, the shorter NF-YA splice variant is abundantly expressed and sustains their expansion. Here, we report that satellite cells, the stem cell population of adult skeletal muscle necessary for its growth and regeneration, express uniquely the longer NF-YA isoform, majorly associated with cell differentiation. Through the generation of a conditional knock out mouse model that selectively deletes the NF-YA gene in satellite cells, we demonstrate that NF-YA expression is fundamental to preserve the pool of muscle stem cells and ensures robust regenerative response to muscle injury. In vivo and ex vivo, satellite cells that survive to NF-YA loss exit the quiescence and are rapidly committed to early differentiation, despite delayed in the progression towards later states. In vitro results demonstrate that NF-YA-depleted muscle stem cells accumulate DNA damage and cannot properly differentiate. These data highlight a new scenario in stem cell biology for NF-Y activity, which is required for efficient myogenic differentiation.

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.

scholarly journals Muscle Satellite Cells: Exploring the Basic Biology to Rule Them

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Camila F. Almeida ◽  
Stephanie A. Fernandes ◽  
Antonio F. Ribeiro Junior ◽  
Oswaldo Keith Okamoto ◽  
Mariz Vainzof
Keyword(s):  
Satellite Cell ◽  
Satellite Cells ◽  
Cell Biology ◽  
Muscle Development ◽  
Cell Activity ◽  
Quiescent State ◽  
Adult Skeletal Muscle ◽  
Resident Stem Cells ◽  
Basic Biology ◽  
Satellite Cell Activity

Adult skeletal muscle is a postmitotic tissue with an enormous capacity to regenerate upon injury. This is accomplished by resident stem cells, named satellite cells, which were identified more than 50 years ago. Since their discovery, many researchers have been concentrating efforts to answer questions about their origin and role in muscle development, the way they contribute to muscle regeneration, and their potential to cell-based therapies. Satellite cells are maintained in a quiescent state and upon requirement are activated, proliferating, and fusing with other cells to form or repair myofibers. In addition, they are able to self-renew and replenish the stem pool. Every phase of satellite cell activity is highly regulated and orchestrated by many molecules and signaling pathways; the elucidation of players and mechanisms involved in satellite cell biology is of extreme importance, being the first step to expose the crucial points that could be modulated to extract the optimal response from these cells in therapeutic strategies. Here, we review the basic aspects about satellite cells biology and briefly discuss recent findings about therapeutic attempts, trying to raise questions about how basic biology could provide a solid scaffold to more successful use of these cells in clinics.

scholarly journals Functional Overload Enhances Satellite Cell Properties in Skeletal Muscle

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Shin Fujimaki ◽  
Masanao Machida ◽  
Tamami Wakabayashi ◽  
Makoto Asashima ◽  
Tohru Takemasa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Physical Exercise ◽  
Resistance Exercise ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Quiescent State ◽  
Proliferative Capacity ◽  
Differentiation Potential ◽  
Activated State

Skeletal muscle represents a plentiful and accessible source of adult stem cells. Skeletal-muscle-derived stem cells, termed satellite cells, play essential roles in postnatal growth, maintenance, repair, and regeneration of skeletal muscle. Although it is well known that the number of satellite cells increases following physical exercise, functional alterations in satellite cells such as proliferative capacity and differentiation efficiency following exercise and their molecular mechanisms remain unclear. Here, we found that functional overload, which is widely used to model resistance exercise, causes skeletal muscle hypertrophy and converts satellite cells from quiescent state to activated state. Our analysis showed that functional overload induces the expression of MyoD in satellite cells and enhances the proliferative capacity and differentiation potential of these cells. The changes in satellite cell properties coincided with the inactivation of Notch signaling and the activation of Wnt signaling and likely involve modulation by transcription factors of the Sox family. These results indicate the effects of resistance exercise on the regulation of satellite cells and provide insight into the molecular mechanism of satellite cell activation following physical exercise.

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.

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 Molecular Regulation and Rejuvenation of Muscle Stem (Satellite) Cell Aging

2015 ◽  
Vol 7 (2) ◽  
pp. 73
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Satellite Cell ◽  
Muscle Mass ◽  
Satellite Cells ◽  
Cell Function ◽  
Muscle Stem Cell ◽  
Muscle Aging ◽  
Age Related

BACKGROUND: Age-related muscle loss leads to lack of muscle strength, resulting in reduced posture and mobility and an increased risk of falls, all of which contribute to a decrease in quality of life. Skeletal muscle regeneration is a complex process, which is not yet completely understood.CONTENT: Skeletal muscle undergoes a progressive age-related loss in mass and function. Preservation of muscle mass depends in part on satellite cells, the resident stem cells of skeletal muscle. Reduced satellite cell function may contribute to the age-associated decrease in muscle mass. Recent studies have delineated that the aging process in organ stem cells is largely caused by age-specific changes in the differentiated niches, and that regenerative outcomes often depend on the age of the niche, rather than on stem cell age. It is likely that epigenetic states will be better define such key satellite cell features as prolonged quiescence and lineage fidelity. It is also likely that DNA and histone modifications will underlie many of the changes in aged satellite cells that account for age-related declines in functionality and rejuvenation through exposure to the systemic environment.SUMMARY: Skeletal muscle aging results in a gradual loss of skeletal muscle mass, skeletal muscle function and regenerative capacity, which can lead to sarcopenia and increased mortality. Although the mechanisms underlying sarcopenia remain unclear, the skeletal muscle stem cell, or satellite cell, is required for muscle regeneration. Decreased muscle stem cell function in aging has long been shown to depend on altered environmental cues, whereas the contribution of intrinsic mechanisms remained less clear. Signals in the aged niche were shown to cause permanent defects in the ability of satellite cells to return to quiescence, ultimately also impairing the maintenance of self-renewing satellite cells. Therefore, only anti-aging strategies taking both factors, the stem cell niche and the stem cells per se, into consideration may ultimately be successful.KEYWORDS: satellite cell, muscle, aging, niche, regenerations

scholarly journals Modulation of HOXA9 after skeletal muscle denervation and reinnervation

2020 ◽  
Author(s):  
Xiaomei Lu ◽  
Bingsheng Liang ◽  
Shuaijie Li ◽  
Zhi Chen ◽  
Wenkai Chang
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Satellite Cells ◽  
Gastrocnemius Muscle ◽  
Myogenic Differentiation ◽  
Cell Activity ◽  
Sham Operation ◽  
Differentiation Potential ◽  
Stem Cell Activity

Abstract Background HOXA9 (Homeobox A9), whose expression is promoted by MLL1 (Mixed Lineage Leukemia 1) and WDR5 (WD-40 repeat protein 5), is a homeodomain-containing transcription factor which plays an essential role in regulating stem cell activity. HOXA9 inhibits regeneration of skeletal muscle and delays the recovery after muscle wound in aged mice, but is little known in denervated/reinnervated muscles. Methods we performed detailed time-process expression analysis on HOXA9 and its promotors, MLL1 and WDR5, in the rat gastrocnemius muscle after three types of sciatic nerve surgeries: nerve transection (denervation); end-to-end repairing (repairing); and the sham operation. Then the specific mechanisms of Hoxa9 were detected in vitro through primary satellite cells transfected respectively by pIRES2-DsRed2 empty plasmids, pIRES2-DsRed2-HOXA9 plasmids, pPLK/ GFP -Puro empty plasmids, and pPLK/GFP-Puro- HOXA9 shRNA plasmids. Results We found that HOXA9 expression was synchronous with the severity of muscle atrophy, as well as the upregulation of MLL1 and WDR5 associated with the denervation state to some extent. Indeed, experiments with primary satellite cells revealed that HOXA9 inhibited myogenic differentiation, but not destroy the differentiation potential, influenced the best-known atrophic pathways, and promoted apoptosis. Conclusion HOXA9 may play a pro-atrophic role in denervated muscle atrophy.

scholarly journals Assessing Autophagy in Muscle Stem Cells

2021 ◽  
Vol 8 ◽  
Author(s):  
Silvia Campanario ◽  
Ignacio Ramírez-Pardo ◽  
Xiaotong Hong ◽  
Joan Isern ◽  
Pura Muñoz-Cánoves
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Rapid Assessment ◽  
Muscle Stem Cells ◽  
Reporter Mice ◽  
Ability To Regenerate ◽  
Resident Stem Cells ◽  
Autophagic Activity

The skeletal muscle tissue in the adult is relatively stable under normal conditions but retains a striking ability to regenerate by its resident stem cells (satellite cells). Satellite cells exist in a quiescent (G0) state; however, in response to an injury, they reenter the cell cycle and start proliferating to provide sufficient progeny to form new myofibers or undergo self-renewal and returning to quiescence. Maintenance of satellite cell quiescence and entry of satellite cells into the activation state requires autophagy, a fundamental degradative and recycling process that preserves cellular proteostasis. With aging, satellite cell regenerative capacity declines, correlating with loss of autophagy. Enhancing autophagy in aged satellite cells restores their regenerative functions, underscoring this proteostatic activity’s relevance for tissue regeneration. Here we describe two strategies for assessing autophagic activity in satellite cells from GFP-LC3 reporter mice, which allows direct autophagosome labeling, or from non-transgenic (wild-type) mice, where autophagosomes can be immunostained. Treatment of GFP-LC3 or WT satellite cells with compounds that interfere with autophagosome-lysosome fusion enables measurement of autophagic activity by flow cytometry and immunofluorescence. Thus, the methods presented permit a relatively rapid assessment of autophagy in stem cells from skeletal muscle in homeostasis and in different pathological scenarios such as regeneration, aging or disease.

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