Methodological issues limit interpretation of negative effects of satellite cell depletion on adult muscle hypertrophy

McCarthy, John J.; Dupont‐Versteegden, Esther E.; Fry, Christopher S.; Murach, Kevin A.; Peterson, Charlotte A.

doi:10.1242/dev.145797

Cited by 34 publications

(31 citation statements)

References 27 publications

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“…Despite a marked shift to larger muscle fibers, a previous investigation from our laboratory showed ~10% increases in average muscle fiber CSA in mature SC+ and SC- mice after 14 days of synergist ablation [4]. We attributed the relatively modest increase in average muscle fiber CSA to a preponderance of newly formed small-caliber muscle fibers, which were revealed by analyzing all fibers in the entire plantaris cross section [4, 27]. Since muscle fiber number increased in both SC+ and SC- mice in that investigation, these new fibers were not exclusively satellite cell-derived.…”

Section: Discussionmentioning

confidence: 93%

“…Utilizing the Pax7 CreER -R26R DTA tamoxifen-inducible mouse model, our laboratory showed similar hypertrophic responses in vehicle-treated (satellite cell-replete, SC+) versus tamoxifen-treated (satellite cell-depleted, SC-) adult mice after 2 weeks of mechanical overload of the plantaris [4, 27]. We subsequently found that resident myonuclei in adult SC- mice can robustly up-regulate transcriptional output to meet biosynthetic demands during the early phase of hypertrophy [26].…”

Section: Introductionmentioning

confidence: 99%

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Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice

et al. 2017

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BackgroundPax7+ satellite cells are required for skeletal muscle fiber growth during post-natal development in mice. Satellite cell-mediated myonuclear accretion also appears to persist into early adulthood. Given the important role of satellite cells during muscle development, we hypothesized that the necessity of satellite cells for adaptation to an imposed hypertrophic stimulus depends on maturational age.MethodsPax7CreER-R26RDTA mice were treated for 5 days with vehicle (satellite cell-replete, SC+) or tamoxifen (satellite cell-depleted, SC-) at 2 months (young) and 4 months (mature) of age. Following a 2-week washout, mice were subjected to sham surgery or 10 day synergist ablation overload of the plantaris (n = 6–9 per group). The surgical approach minimized regeneration, de novo fiber formation, and fiber splitting while promoting muscle fiber growth. Satellite cell density (Pax7+ cells/fiber), embryonic myosin heavy chain expression (eMyHC), and muscle fiber cross sectional area (CSA) were evaluated via immunohistochemistry. Myonuclei (myonuclei/100 mm) were counted on isolated single muscle fibers.ResultsTamoxifen treatment depleted satellite cells by ≥90% and prevented myonuclear accretion with overload in young and mature mice (p < 0.05). Satellite cells did not recover in SC- mice after overload. Average muscle fiber CSA increased ~20% in young SC+ (p = 0.07), mature SC+ (p < 0.05), and mature SC- mice (p < 0.05). In contrast, muscle fiber hypertrophy was prevented in young SC- mice. Muscle fiber number increased only in mature mice after overload (p < 0.05), and eMyHC expression was variable, specifically in mature SC+ mice.ConclusionsReliance on satellite cells for overload-induced hypertrophy is dependent on maturational age, and global responses to overload differ in young versus mature mice.Electronic supplementary materialThe online version of this article (doi:10.1186/s13395-017-0132-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice

et al. 2017

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“…Future studies will need to reveal the exact contribution of both mechanisms to exercise-induced myonuclear accumulation. Whether SCs are required for muscle hypertrophy is a heavily debated topic [51] and likely depends on age, genetic mutation, models used to induce hypertrophy and time of sampling after the applied stimulus [6,8,[19][20][21]25,52,53]. Moreover, impairing SC contribution by the frequently used Pax7 CreER-DTA model might evoke undesirable adaptations such as impairments of proprioception and reduced voluntary wheel running, which do not re ect physiological circumstances [16].…”

Section: Discussionmentioning

confidence: 99%

Exercise promotes satellite cell contribution to myofibers in a load-dependent manner

Masschelein

D’Hulst

Zvick

et al. 2020

Preprint

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Background Satellite cells (SCs) are required for muscle repair following injury and are involved in muscle remodeling upon muscular contractions. Exercise stimulates SC accumulation and myonuclear accretion. To what extent exercise training at different mechanical loads drive SC contribution to myonuclei however is unknown. Results By performing SC fate tracing experiments, we show that 8-weeks of voluntary wheel running increased SC contribution to myofibers in mouse plantar flexor muscles in a load-dependent but fiber type-independent manner. Increased SC fusion however was not exclusively linked to muscle hypertrophy as wheel running without external load substantially increased SC fusion in the absence of fiber hypertrophy. Due to nuclear propagation, nuclear fluorescent fate tracing mouse models were inadequate to quantify SC contribution to myonuclei. Ultimately, by performing fate tracing at the DNA level, we show that SC contribution mirrors myonuclear accretion during exercise. Conclusions Collectively, mechanical load during exercise independently promotes SC contribution to existing myofibers. Also, due to propagation of nuclear fluorescent reporter proteins, our data warrant caution for the use of exisiting reporter mouse models for the quantitative evaluation of satellite cell contribution to myonuclei.

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“…Whether SCs are required for muscle hypertrophy is a heavily debated topic [40] and likely depends on age, genetic mutation, models used to induce hypertrophy and time of sampling after the applied stimulus [6,8,[19][20][21]25]. Moreover, impairing SC contribution by the frequently used Pax7 CreER − DTA model might evoke undesirable adaptations such as impairments of proprioception and reduced voluntary wheel running, which do not reflect physiological circumstances [16].…”

Section: Discussionmentioning

confidence: 99%

“…Mice have a strong intrinsic drive to run large distances in their active phase [18], which keeps stress and mouse handling at a minimum. Furthermore, by applying resistance to the running wheel, muscle hypertrophy can be induced without substantial muscle damage [19][20][21][22][23][24][25] and reducing wheel resistance (free running) leads to favorable endurance adaptations without pronounced effects on muscle hypertrophy [16,26]. Thus, using this exercise model in combination with genetic lineage tracing experiments of SCs, we aimed to evaluate whether SC contribution to myonuclei is mediated by increasing load during exercise training and whether this manifests in SCmediated myonuclear accretion.…”

Section: Introductionmentioning

confidence: 99%

Exercise promotes satellite cell contribution to myofibers in a load-dependent manner

Masschelein

D’Hulst

Zvick

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Satellite cells (SCs) are required for muscle repair following injury and are involved in muscle remodeling upon muscular contractions. Exercise stimulates SC accumulation and myonuclear accretion. To what extent exercise training at different mechanical loads drive SC contribution to myonuclei however is unknown. Results By performing SC fate tracing experiments, we show that 8-weeks of voluntary wheel running increased SC contribution to myonuclei in mouse plantar flexor muscles in a load-dependent but fiber type-independent manner. Increased SC fusion however was not exclusively linked to muscle hypertrophy as wheel running without external load substantially increased SC fusion in the absence of fiber hypertrophy. Due to nuclear propagation, nuclear fluorescent fate tracing mouse models were inadequate to quantify SC contribution to myonuclei. Ultimately, by performing fate tracing at the DNA level, we show that SC contribution mirrors myonuclear accretion during exercise. Conclusions Collectively, these findings provide direct evidence that mechanical load during exercise independently promotes SC contribution to existing myofibers.

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Methodological issues limit interpretation of negative effects of satellite cell depletion on adult muscle hypertrophy

Cited by 34 publications

References 27 publications

Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice

Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice

Exercise promotes satellite cell contribution to myofibers in a load-dependent manner

Exercise promotes satellite cell contribution to myofibers in a load-dependent manner

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