scholarly journals Depletion of resident muscle stem cells inhibits muscle fiber hypertrophy induced by lifelong physical activity

2019 ◽  
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 ◽  
Muscle Growth ◽  
Free Access ◽  
Running Wheel ◽  
Hypertrophic Growth

AbstractBackgroundA reduction in skeletal muscle stem cell (satellite cell) content with advancing age is thought to directly contribute to the progressive loss of skeletal muscle mass and function with aging (sarcopenia). However, we reported that the depletion of satellite cells throughout adulthood did not affect the onset or degree of sarcopenia observed in sedentary old mice. The current study was designed to determine if lifelong physical activity would alter the requirements for satellite cells during aging.MethodsWe administered vehicle or tamoxifen to adult (5 months old) female Pax7-DTA mice for 5 consecutive days to effectively deplete satellite cells. Following a 2-month washout period, mice were assigned to physically active (free access to a running wheel) or sedentary (locked running wheel) conditions. Thirteen months later, at a mean age of 20 months, mice were sacrificed for subsequent analysis.ResultsSatellite cell depletion throughout adulthood negatively impacted physical function and limited muscle fiber hypertrophy in response to lifelong physical activity. To further interrogate these findings, we performed transcriptome-wide analyses on the hind limb muscles that experienced hypertrophic growth (plantaris and soleus) in response to lifelong physical activity. Our findings demonstrate that satellite cell function is muscle type-specific; fusion with fibers is apparent in oxidative muscles, while initiation of Gαi2 signaling appears to require satellite cells in glycolytic muscles to induce muscle growth..ConclusionsThese findings suggest that satellite cells, or their secretory products, are viable therapeutic targets to preserve physical function with aging and promote muscle growth in older adults who regularly engage in physical activity.

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 Satellite Cell Depletion Disrupts Transcriptional Coordination and Muscle Adaptation to Exercise

Function ◽  
2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Davis A Englund ◽  
Vandré C Figueiredo ◽  
Cory M Dungan ◽  
Kevin A Murach ◽  
Bailey D Peck ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Gene Networks ◽  
Wheel Running ◽  
Skeletal Muscle Regeneration ◽  
Rna Seq ◽  
Muscle Adaptation ◽  
Hypertrophic Growth ◽  
Adaptation To Exercise

Abstract Satellite cells are required for postnatal development, skeletal muscle regeneration across the lifespan, and skeletal muscle hypertrophy prior to maturity. Our group has aimed to address whether satellite cells are required for hypertrophic growth in mature skeletal muscle. Here, we generated a comprehensive characterization and transcriptome-wide profiling of skeletal muscle during adaptation to exercise in the presence or absence of satellite cells in order to identify distinct phenotypes and gene networks influenced by satellite cell content. We administered vehicle or tamoxifen to adult Pax7-DTA mice and subjected them to progressive weighted wheel running (PoWeR). We then performed immunohistochemical analysis and whole-muscle RNA-seq of vehicle (SC+) and tamoxifen-treated (SC−) mice. Further, we performed single myonuclear RNA-seq to provide detailed information on how satellite cell fusion affects myonuclear transcription. We show that while skeletal muscle can mount a robust hypertrophic response to PoWeR in the absence of satellite cells, growth, and adaptation are ultimately blunted. Transcriptional profiling reveals several gene networks key to muscle adaptation are altered in the absence of satellite cells.

scholarly journals Starring or Supporting Role? Satellite Cells and Skeletal Muscle Fiber Size Regulation

Physiology ◽  
2018 ◽  
Vol 33 (1) ◽  
pp. 26-38 ◽  
Author(s):  
Kevin A. Murach ◽  
Christopher S. Fry ◽  
Tyler J. Kirby ◽  
Janna R. Jackson ◽  
Jonah D. Lee ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Satellite Cell ◽  
Muscle Fiber ◽  
Satellite Cells ◽  
Skeletal Muscle Fiber ◽  
Cell Depletion ◽  
Loss Of Function ◽  
Adult Mice ◽  
Fiber Size

Recent loss-of-function studies show that satellite cell depletion does not promote sarcopenia or unloading-induced atrophy, and does not prevent regrowth. Although overload-induced muscle fiber hypertrophy is normally associated with satellite cell-mediated myonuclear accretion, hypertrophic adaptation proceeds in the absence of satellite cells in fully grown adult mice, but not in young growing mice. Emerging evidence also indicates that satellite cells play an important role in remodeling the extracellular matrix during hypertrophy.

scholarly journals Reduced Notch signalling leads to postnatal skeletal muscle hypertrophy in Pofut1 cax/cax mice

Open Biology ◽  
2016 ◽  
Vol 6 (9) ◽  
pp. 160211 ◽  
Author(s):  
Bilal Al Jaam ◽  
Katy Heu ◽  
Florian Pennarubia ◽  
Alexandre Segelle ◽  
Laetitia Magnol ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Muscle Hypertrophy ◽  
Target Genes ◽  
Muscle Growth ◽  
Notch Signalling ◽  
Quiescent State ◽  
Notch Receptors

Postnatal skeletal muscle growth results from the activation of satellite cells and/or an increase in protein synthesis. The Notch signalling pathway maintains satellite cells in a quiescent state, and once activated, sustains their proliferation and commitment towards differentiation. In mammals, POFUT1-mediated O -fucosylation regulates the interactions between NOTCH receptors and ligands of the DELTA/JAGGED family, thus initiating the activation of canonical Notch signalling. Here, we analysed the consequences of downregulated expression of the Pofut1 gene on postnatal muscle growth in mutant Pofut1 cax/cax (cax, compact axial skeleton) mice and differentiation of their satellite cell-derived myoblasts (SCDMs). Pofut1 cax/cax mice exhibited muscle hypertrophy, no hyperplasia and a decrease in satellite cell numbers compared with wild-type C3H mice. In agreement with these observations, Pofut1 cax/cax SCDMs differentiated earlier concomitant with reduced Pax7 expression and decrease in PAX7 + /MYOD − progenitor cells. In vitro binding assays showed a reduced interaction of DELTA-LIKE 1 ligand (DLL1) with NOTCH receptors expressed at the cell surface of SCDMs, leading to a decreased Notch signalling as seen by the quantification of cleaved NICD and Notch target genes. These results demonstrated that POFUT1-mediated O- fucosylation of NOTCH receptors regulates myogenic cell differentiation and affects postnatal muscle growth in mice.

scholarly journals Effects of Testosterone Supplementation on Skeletal Muscle Fiber Hypertrophy and Satellite Cells in Community-Dwelling Older Men

2006 ◽  
Vol 91 (8) ◽  
pp. 3024-3033 ◽  
Author(s):  
Indrani Sinha-Hikim ◽  
Marcia Cornford ◽  
Hilda Gaytan ◽  
Martin L. Lee ◽  
Shalender Bhasin
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Muscle Fiber ◽  
Satellite Cells ◽  
Older Men ◽  
Cell Number ◽  
Community Dwelling ◽  
Testosterone Treatment ◽  
Testosterone Administration ◽  
Dose Dependent

Abstract Objective: In this study, we determined the effects of graded doses of testosterone on muscle fiber cross-sectional area (CSA) and satellite cell number and replication in older men. Participants: Healthy men, 60–75 yr old, received a long-acting GnRH agonist to suppress endogenous testosterone production and 25, 50, 125, 300, or 600 mg testosterone enanthate im weekly for 20 wk. Methods: Immunohistochemistry, light and confocal microscopy, and electron microscopy were used to perform fiber typing and quantitate myonuclear and satellite cell number in vastus lateralis biopsies, obtained before and after 20 wk of treatment. Results: Testosterone administration in older men was associated with dose-dependent increases in CSA of both types I and II fibers. Satellite cell number increased dose dependently at the three highest doses (3% at baseline vs. 6.2, 9.2, and 13.0% at 125, 300, and 600 mg doses, P < 0.05). Testosterone administration was associated with an increase in the number of proliferating cell nuclear antigen+ satellite cells (1.8% at baseline vs. 3.9, 7.5, and 13% at 125, 300, and 600 mg doses, P < 0.005). The expression of activated Notch, examined only in the 300-mg group (baseline, 2.3 vs. 9.0% after treatment, P < 0.005), increased in satellite cells after testosterone treatment. The expression of myogenin (baseline, 6.2 vs. 20.7% after treatment, P < 0.005), examined only in the 300-mg group, increased significantly in muscle fiber nuclei after testosterone treatment, but Numb expression did not change. Conclusions: Older men respond to graded doses of testosterone with a dose-dependent increase in muscle fiber CSA and satellite cell number. Testosterone-induced skeletal muscle hypertrophy in older men is associated with increased satellite cell replication and activation.

scholarly journals Continuous Feeding Does Not Blunt Satellite Cell Abundance, Myonuclear Accretion, or Lean Growth in a Neonatal Piglet Model of Prematurity

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 696-696
Author(s):  
Marko Rudar ◽  
Jane Naberhuis ◽  
Agus Suryawan ◽  
Hanh Nguyen ◽  
Candace Style ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Muscle Fiber ◽  
Muscle Growth ◽  
Preterm Neonates ◽  
Proliferating Cells ◽  
Cross Sectional ◽  
Orogastric Tube ◽  
Skeletal Muscle Growth ◽  
Lean Growth

Abstract Objectives Lean growth in preterm neonates is poor and may increase the lifelong risk for adverse health outcomes. Strategies are needed to promote skeletal muscle growth in the postnatal period. Skeletal muscle growth, which accounts for the largest fraction of lean mass accretion, requires the coordinated activation of protein synthesis, satellite cell (SC; muscle stem cell) proliferation, differentiation, and fusion into muscle fibers. The objective of this study was to determine the effect of feeding modality on SC abundance, myonuclear accretion, and lean growth in preterm neonatal pigs. Methods Pigs delivered 10 d preterm by C-section (952 ± 205 g) were fitted with an umbilical artery catheter (later replaced with jugular vein catheter) and an orogastric tube for parenteral and enteral nutrition, respectively. Pigs were assigned to continuous (CONT; n = 14; 7.5 mL/[kg·h]) or intermittent bolus (INT; n = 30; 30 mL/kg every 4 h) feeding for 21 d (210 kcal/kg and 16 g protein/kg per d); pigs were advanced from parenteral to enteral feeding over 6 d. Bromodeoxyuridine (BrdU; 25 mg·kg−1) was administered to pigs every 12 h from days 19 to 20, inclusive, to label proliferating cells. Body composition was measured by DXA on day 21. Satellite cell (Pax7+) abundance, myonuclear accretion, and muscle fiber cross-sectional area (CSA) were quantified in the longissimus dorsi muscle by immunofluorescence. Results Sublaminal Pax7+ SC abundance was similar between CONT and INT groups (60.9 vs. 58.3 ± 6.0 per 1000 fibers). The proportion of sublaminal relative to total Pax7+ SCs was similar between CONT and INT groups (78.8 vs. 78.8 ± 2.2%). The abundance of BrdU + myonuclei, an index of myonuclear accretion, did not differ between CONT and INT groups (26.7 vs. 26.7 ± 3.4 per 1000 fibers). Total myonuclei did not differ between CONT and INT groups (420 vs. 403 ± 16 per 1000 fibers). Muscle fiber CSA did not differ between CONT and INT groups (210 vs. 237 ± 15 µm2). Lean and fat masses were similar between groups. Conclusions Unlike term pigs, CONT feeding does not blunt lean growth in preterm pigs compared to INT feeding. The absence of increased lean growth with INT feeding is consistent with the similar SC abundance, myonuclear accretion, and muscle fiber CSA between feeding modalities. Funding Sources Research was supported by NIH and USDA.

scholarly journals Skeletal muscle fiber size and fiber type distribution in human cancer: Effects of weight loss and relationship to physical function

2016 ◽  
Vol 35 (6) ◽  
pp. 1359-1365 ◽  
Author(s):  
Michael J. Toth ◽  
Damien M. Callahan ◽  
Mark S. Miller ◽  
Timothy W. Tourville ◽  
Sarah B. Hackett ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Physical Function ◽  
Muscle Fiber ◽  
Human Cancer ◽  
Fiber Type ◽  
Skeletal Muscle Fiber ◽  
Type Distribution ◽  
Fiber Size ◽  
Fiber Type Distribution

Mechanical load-dependent regulation of satellite cell and fiber size in rat soleus muscle

2006 ◽  
Vol 290 (4) ◽  
pp. C981-C989 ◽  
Author(s):  
X. D. Wang ◽  
F. Kawano ◽  
Y. Matsuoka ◽  
K. Fukunaga ◽  
M. Terada ◽  
...  
Keyword(s):  
Satellite Cell ◽  
Muscle Fiber ◽  
Satellite Cells ◽  
Central Region ◽  
Sarcomere Length ◽  
Sectional Area ◽  
Cross Sectional ◽  
Fiber Properties ◽  
Rat Soleus Muscle ◽  
The Mean

The effects of mechanical unloading and reloading on the properties of rat soleus muscle fibers were investigated in male Wistar Hannover rats. Satellite cells in the fibers of control rats were distributed evenly throughout the fiber length. After 16 days of hindlimb unloading, the number of satellite cells in the central, but not the proximal or distal, region of the fiber was decreased. The number of satellite cells in the central region gradually increased during the 16-day period of reloading. The mean sarcomere length in the central region of the fibers was passively shortened during unloading due to the plantarflexed position at the ankle joint: sarcomere length was maintained at <2.1 μm, which is a critical length for tension development. Myonuclear number and domain size, fiber cross-sectional area, and the total number of mitotically active and quiescent satellite cells of whole muscle fibers were lower than control fibers after 16 days of unloading. These values then returned to control values after 16 days of reloading. These results suggest that satellite cells play an important role in the regulation of muscle fiber properties. The data also indicate that the satellite cell-related regulation of muscle fiber properties is dependent on the level of mechanical loading, which, in turn, is influenced by the mean sarcomere length. However, it is still unclear why the region-specific responses, which were obvious in satellite cells, were not induced in myonuclear number and fiber cross-sectional area.

scholarly journals Prepubertal skeletal muscle growth requires Pax7-expressing satellite cell-derived myonuclear contribution

Development ◽  
2018 ◽  
Vol 145 (20) ◽  
pp. dev167197 ◽  
Author(s):  
John F. Bachman ◽  
Alanna Klose ◽  
Wenxuan Liu ◽  
Nicole D. Paris ◽  
Roméo S. Blanc ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Muscle Growth ◽  
Skeletal Muscle Growth

Implication of the satellite cell in dystrophic muscle fibrosis: a self-perpetuating mechanism of collagen overproduction

2007 ◽  
Vol 293 (2) ◽  
pp. C661-C669 ◽  
Author(s):  
Catherine Alexakis ◽  
Terence Partridge ◽  
George Bou-Gharios
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Collagen Type ◽  
Collagen Type I ◽  
C2c12 Cells ◽  
Type I ◽  
Wild Type ◽  
Dystrophic Muscle ◽  
Type Iii

Because of its mechanical function, skeletal muscle is heavily influenced by the composition of its extracellular matrix (ECM). Fibrosis generated by chronic damage, such as occurs in muscular dystrophies, is thus particularly disastrous in this tissue. Here, we examined the interrelationship between the muscle satellite cell and the production of collagen type I, a major component of fibrotic ECM, by using both C2C12, a satellite cell-derived cell line, and primary muscle satellite cells. In C2C12 cells, we found that expression of collagen type I mRNA decreases substantially during skeletal muscle differentiation. On a single-cell level, collagen type I and myogenin became mutually exclusive after 3 days in differentiation medium, whereas addition of collagen markedly suppressed differentiation of C2C12 cells. Primary cultures of satellite cells associated with isolated single fibers of the young (4 wk old) mdx dystrophic mouse and of C57BL/10ScSn wild-type controls expressed collagen type I and type III mRNA and protein. This pattern persisted in wild-type mice at all ages. But, curiously, in older (18-mo-old) mdx mice, although the myogenic cells continued to express type III collagen, type I expression became restricted to nonmyogenic cells. These cells typically constituted part of a cellular sheet surrounding the old mdx fibers. This combination of features strongly suggests that the progression to fibrosis in dystrophic muscle involves changes in the mechanisms controlling matrix production, which generates positive feedback that results in a reprogramming of myoblasts to a profibrotic function.

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