scholarly journals Muscle satellite cells adopt divergent fates

2004 ◽  
Vol 166 (3) ◽  
pp. 347-357 ◽  
Author(s):  
Peter S. Zammit ◽  
Jon P. Golding ◽  
Yosuke Nagata ◽  
Valérie Hudon ◽  
Terence A. Partridge ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Cell Phenotype ◽  
Proliferating Cells ◽  
Cell Compartment ◽  
Adult Skeletal Muscle ◽  
Muscle Stem Cells ◽  
Cell Pool

Growth, repair, and regeneration of adult skeletal muscle depends on the persistence of satellite cells: muscle stem cells resident beneath the basal lamina that surrounds each myofiber. However, how the satellite cell compartment is maintained is unclear. Here, we use cultured myofibers to model muscle regeneration and show that satellite cells adopt divergent fates. Quiescent satellite cells are synchronously activated to coexpress the transcription factors Pax7 and MyoD. Most then proliferate, down-regulate Pax7, and differentiate. In contrast, other proliferating cells maintain Pax7 but lose MyoD and withdraw from immediate differentiation. These cells are typically located in clusters, together with Pax7−ve progeny destined for differentiation. Some of the Pax7+ve/MyoD−ve cells then leave the cell cycle, thus regaining the quiescent satellite cell phenotype. Significantly, noncycling cells contained within a cluster can be stimulated to proliferate again. These observations suggest that satellite cells either differentiate or switch from terminal myogenesis to maintain the satellite cell pool.

scholarly journals Canonical NF-κB signaling regulates satellite stem cell homeostasis and function during regenerative myogenesis

2018 ◽  
Vol 11 (1) ◽  
pp. 53-66 ◽  
Author(s):  
Alex R Straughn ◽  
Sajedah M Hindi ◽  
Guangyan Xiong ◽  
Ashok Kumar
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Cell Function ◽  
Skeletal Muscle Regeneration ◽  
Cell Homeostasis ◽  
Adult Skeletal Muscle ◽  
Adult Mice ◽  
And Function

Abstract Skeletal muscle regeneration in adults is attributed to the presence of satellite stem cells that proliferate, differentiate, and eventually fuse with injured myofibers. However, the signaling mechanisms that regulate satellite cell homeostasis and function remain less understood. While IKKβ-mediated canonical NF-κB signaling has been implicated in the regulation of myogenesis and skeletal muscle mass, its role in the regulation of satellite cell function during muscle regeneration has not been fully elucidated. Here, we report that canonical NF-κB signaling is induced in skeletal muscle upon injury. Satellite cell-specific inducible ablation of IKKβ attenuates skeletal muscle regeneration in adult mice. Targeted ablation of IKKβ also reduces the number of satellite cells in injured skeletal muscle of adult mice, potentially through inhibiting their proliferation and survival. We also demonstrate that the inhibition of specific components of the canonical NF-κB pathway causes precocious differentiation of cultured satellite cells both ex vivo and in vitro. Finally, our results highlight that the constitutive activation of canonical NF-κB signaling in satellite cells also attenuates skeletal muscle regeneration following injury in adult mice. Collectively, our study demonstrates that the proper regulation of canonical NF-κB signaling is important for the regeneration of adult skeletal muscle.

scholarly journals Depletion of resident muscle stem cells negatively impacts running volume, physical function, and muscle fiber hypertrophy in response to lifelong physical activity

2020 ◽  
Vol 318 (6) ◽  
pp. C1178-C1188 ◽  
Author(s):  
Davis A. Englund ◽  
Kevin A. Murach ◽  
Cory M. Dungan ◽  
Vandré C. Figueiredo ◽  
Ivan J. Vechetti ◽  
...  
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Physical Function ◽  
Satellite Cell ◽  
Muscle Fiber ◽  
Satellite Cells ◽  
Cell Depletion ◽  
Muscle Adaptation ◽  
Adult Skeletal Muscle

To date, studies that have aimed to investigate the role of satellite cells during adult skeletal muscle adaptation and hypertrophy have utilized a nontranslational stimulus and/or have been performed over a relatively short time frame. Although it has been shown that satellite cell depletion throughout adulthood does not drive skeletal muscle loss in sedentary mice, it remains unknown how satellite cells participate in skeletal muscle adaptation to long-term physical activity. The current study was designed to determine whether reduced satellite cell content throughout adulthood would influence the transcriptome-wide response to physical activity and diminish the adaptive response of skeletal muscle. We administered vehicle or tamoxifen to adult Pax7-diphtheria toxin A (DTA) mice to deplete satellite cells and assigned them to sedentary or wheel-running conditions for 13 mo. Satellite cell depletion throughout adulthood reduced balance and coordination, overall running volume, and the size of muscle proprioceptors (spindle fibers). Furthermore, satellite cell participation was necessary for optimal muscle fiber hypertrophy but not adaptations in fiber type distribution in response to lifelong physical activity. Transcriptome-wide analysis of the plantaris and soleus revealed that satellite cell function is muscle type specific; satellite cell-dependent myonuclear accretion was apparent in oxidative muscles, whereas initiation of G protein-coupled receptor (GPCR) signaling in the glycolytic plantaris may require satellite cells to induce optimal adaptations to long-term physical activity. These findings suggest that satellite cells play a role in preserving physical function during aging and influence muscle adaptation during sustained periods of physical activity.

scholarly journals Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration

Development ◽  
2011 ◽  
Vol 138 (19) ◽  
pp. 4333-4333 ◽  
Author(s):  
R. Sambasivan ◽  
R. Yao ◽  
A. Kissenpfennig ◽  
L. Van Wittenberghe ◽  
A. Paldi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Adult Skeletal Muscle

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.

scholarly journals Pro-myogenic small molecules revealed by a chemical screen on primary muscle stem cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sean M. Buchanan ◽  
Feodor D. Price ◽  
Alessandra Castiglioni ◽  
Amanda Wagner Gee ◽  
Joel Schneider ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Small Molecules ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Muscle Repair ◽  
Muscle Stem Cells

Abstract Satellite cells are the canonical muscle stem cells that regenerate damaged skeletal muscle. Loss of function of these cells has been linked to reduced muscle repair capacity and compromised muscle health in acute muscle injury and congenital neuromuscular diseases. To identify new pathways that can prevent loss of skeletal muscle function or enhance regenerative potential, we established an imaging-based screen capable of identifying small molecules that promote the expansion of freshly isolated satellite cells. We found several classes of receptor tyrosine kinase (RTK) inhibitors that increased freshly isolated satellite cell numbers in vitro. Further exploration of one of these compounds, the RTK inhibitor CEP-701 (also known as lestaurtinib), revealed potent activity on mouse satellite cells both in vitro and in vivo. This expansion potential was not seen upon exposure of proliferating committed myoblasts or non-myogenic fibroblasts to CEP-701. When delivered subcutaneously to acutely injured animals, CEP-701 increased both the total number of satellite cells and the rate of muscle repair, as revealed by an increased cross-sectional area of regenerating fibers. Moreover, freshly isolated satellite cells expanded ex vivo in the presence of CEP-701 displayed enhanced muscle engraftment potential upon in vivo transplantation. We provide compelling evidence that certain RTKs, and in particular RET, regulate satellite cell expansion during muscle regeneration. This study demonstrates the power of small molecule screens of even rare adult stem cell populations for identifying stem cell-targeting compounds with therapeutic potential.

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.

Cellular and Molecular Regulation of Muscle Regeneration

2004 ◽  
Vol 84 (1) ◽  
pp. 209-238 ◽  
Author(s):  
SOPHIE B. P. CHARGÉ ◽  
MICHAEL A. RUDNICKI
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Satellite Cell ◽  
Muscle Regeneration ◽  
Adult Stem Cells ◽  
Cell Activation ◽  
De Novo ◽  
Molecular Regulation ◽  
Muscle Repair ◽  
Adult Skeletal Muscle

Chargé, Sophie B. P., and Michael A. Rudnicki. Cellular and Molecular Regulation of Muscle Regeneration. Physiol Rev 84: 209–238, 2004; 10.1152/physrev.00019.2003.—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.

scholarly journals Brain-derived Neurotrophic Factor Regulates Satellite Cell Differentiation and Skeltal Muscle Regeneration

2010 ◽  
Vol 21 (13) ◽  
pp. 2182-2190 ◽  
Author(s):  
Charlene Clow ◽  
Bernard J. Jasmin
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Neurotrophic Factor ◽  
Cell Function ◽  
Brain Derived Neurotrophic Factor ◽  
Postnatal Growth ◽  
Adult Skeletal Muscle

In adult skeletal muscle, brain-derived neurotrophic factor (BDNF) is expressed in myogenic progenitors known as satellite cells. To functionally address the role of BDNF in muscle satellite cells and regeneration in vivo, we generated a mouse in which BDNF is specifically depleted from skeletal muscle cells. For comparative purposes, and to determine the specific role of muscle-derived BDNF, we also examined muscles of the complete BDNF−/− mouse. In both models, expression of the satellite cell marker Pax7 was significantly decreased. Furthermore, proliferation and differentiation of primary myoblasts was abnormal, exhibiting delayed induction of several markers of differentiation as well as decreased myotube size. Treatment with exogenous BDNF protein was sufficient to rescue normal gene expression and myotube size. Because satellite cells are responsible for postnatal growth and repair of skeletal muscle, we next examined whether regenerative capacity was compromised. After injury, BDNF-depleted muscle showed delayed expression of several molecular markers of regeneration, as well as delayed appearance of newly regenerated fibers. Recovery of wild-type BDNF levels was sufficient to restore normal regeneration. Together, these findings suggest that BDNF plays an important role in regulating satellite cell function and regeneration in vivo, particularly during early stages.

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