Kinetics of Myoblast Proliferation Show That Resident Satellite Cells Are Competent to Fully Regenerate Skeletal Muscle Fibers

Zammit, Peter S.; Heslop, Louise A.; Hudon, Valérie; Rosenblatt, J. D.; Tajbakhsh, Shahragim; Buckingham, Margaret; Beauchamp, Jonathan R.; Partridge, Terence A.

doi:10.1006/excr.2002.5653

Cited by 259 publications

(209 citation statements)

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“…Although this finding has interesting implications for use in adult stem cell therapy, it does not demonstrate that such reprogramming plays a significant role in muscle regeneration. Indeed, a recent report by Zammit et al (2002) showed that activation of myofiber-associated satellite cells is sufficient to fully regenerate skeletal muscle fibers. In this respect, we show here in both established cell lines and primary human myoblasts that the activation of muscle differentiation and hypertrophy involves a cooperative effect of insulin and Wnt-dependent inactivation of GSK-3.…”

Section: Wnt and Insulin Signaling Pathways Have Synergistic Effects mentioning

confidence: 99%

Insulin and Wnt1 Pathways Cooperate to Induce Reserve Cell Activation in Differentiation and Myotube Hypertrophy

Rochat

Fernandez

Vandromme

et al. 2004

MBoC

132

115

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During ex vivo myoblast differentiation, a pool of quiescent mononucleated myoblasts, reserve cells, arise alongside myotubes. Insulin/insulin-like growth factor (IGF) and PKB/Akt-dependent phosphorylation activates skeletal muscle differentiation and hypertrophy. We have investigated the role of glycogen synthase kinase 3 (GSK-3) inhibition by protein kinase B (PKB)/Akt and Wnt/␤-catenin pathways in reserve cell activation during myoblast differentiation and myotube hypertrophy. Inhibition of GSK-3 by LiCl or SB216763, restored insulin-dependent differentiation of C2ind myoblasts in low serum, and cooperated with insulin in serum-free medium to induce MyoD and myogenin expression in C2ind myoblasts, quiescent C2 or primary human reserve cells. We show that LiCl treatment induced nuclear accumulation of ␤-catenin in C2 myoblasts, thus mimicking activation of canonical Wnt signaling. Similarly to the effect of GSK-3 inhibitors with insulin, coculturing C2 reserve cells with Wnt1-expressing fibroblasts enhanced insulinstimulated induction of MyoD and myogenin in reserve cells. A similar cooperative effect of LiCl or Wnt1 with insulin was observed during late ex vivo differentiation and promoted increased size and fusion of myotubes. We show that this synergistic effect on myotube hypertrophy involved an increased fusion of reserve cells into preexisting myotubes. These data reveal insulin and Wnt/␤-catenin pathways cooperate in muscle cell differentiation through activation and recruitment of satellite cell-like reserve myoblasts. INTRODUCTIONSatellite cells are skeletal muscle adult stem cells that participate in postnatal muscle growth and regeneration. Although satellite cells are normally quiescent in adult muscle, they are responsible for muscle regeneration after injury and involved in work-or load-induced muscle fiber hypertrophy (Rosenblatt and Parry, 1992;Schultz and McCormick, 1994;De Angelis et al., 1999;Semsarian et al., 1999;Bodine et al., 2001).Ex vivo models such as myogenic cell lines were isolated from adult mouse muscle and as such are derived from adult satellite cells. At the proliferative stage, myoblasts (activated satellite cells) can be grown extensively in high serum-containing medium and express MyoD, a musclespecific transcription factor that regulates the differentiation process (Weintraub, 1993). When serum levels are lowered, myoblasts exit the cell cycle and spontaneously differentiate, giving rise to a heterogeneous population of cells. The first and major subpopulation is composed of myotubes, quiescent multinucleated cells expressing muscle-specific structural proteins. The remaining subset is composed of quiescent, mononucleated and undifferentiated cells termed reserve cells. Reserve cells retain the ability to be activated and proliferate after which they can be induced to differentiate, leading again to a new mixed population of myotubes and reserve cells. They also express at least two genes characteristic of skeletal muscle stem cells, namely, myf-5 and cd34 and from these c...

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Section: Wnt and Insulin Signaling Pathways Have Synergistic Effects mentioning

confidence: 99%

Insulin and Wnt1 Pathways Cooperate to Induce Reserve Cell Activation in Differentiation and Myotube Hypertrophy

Rochat

Fernandez

Vandromme

et al. 2004

MBoC

132

115

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“…For example, muscle stem cells (satellite cells) are required for the regeneration of myofibers following injury or transplantation in humans and mice (Schultz et al, 1978;Zammit et al, 2002;Morgan and Partridge, 2003;Sacco et al, 2008;Corbu et al, 2010). Even for tissues with low turnover and regenerative capacity in response to injury, such as the brain, stem cells may play important roles in the adaptive nature of the tissue.…”

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confidence: 99%

Epigenetic regulation of aging stem cells

2011

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“…We recently made the unexpected observation that the Myf5 locus can be routinely reactivated in the myonuclei of EDL myofibres during culture (Zammit et al, 2002). Although previous studies have reported increased levels of Myf5 transcript in denervated muscle (Buonanno et al,Fig.…”

Section: Denervation Leads To the Reactivation Of The Myf5 Locus In Mmentioning

confidence: 98%

“…During development in the Myf5 nlacZ/+ mouse, h-galactosidase is detectable in both myoblasts and myonuclei (Tajbakhsh et al, 1996a) but is subsequently down-regulated so that only quiescent satellite cells remain positive in adult muscle (Beauchamp et al, 2000;Heslop et al, 2001). However, Myf5 (in addition to MyoD and myogenin) is up-regulated during satellite cell activation induced by muscle damage (Cooper et al, 1999;Fuchtbauer and Westphal, 1992;Grounds et al, 1992), a process that can also be modeled in culture (Yablonka-Reuveni and Rivera, 1994;Zammit et al, 2002). Interestingly, culture of Myf5 nlacZ/+ -derived myofibres leads to the rapid reactivation of the Myf5 locus in myonuclei (Zammit et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…However, Myf5 (in addition to MyoD and myogenin) is up-regulated during satellite cell activation induced by muscle damage (Cooper et al, 1999;Fuchtbauer and Westphal, 1992;Grounds et al, 1992), a process that can also be modeled in culture (Yablonka-Reuveni and Rivera, 1994;Zammit et al, 2002). Interestingly, culture of Myf5 nlacZ/+ -derived myofibres leads to the rapid reactivation of the Myf5 locus in myonuclei (Zammit et al, 2002). While the relevance of this observation to the regulation of Myf5 in vivo is unknown, it indicates that the full range of Myf5 expression in adult may not yet have been realised.…”

Section: Introductionmentioning

confidence: 99%

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Myogenic Regulatory Factors

青井重善¹,

下竹孝志²,

津田知樹³

et al. 2012

Encyclopedia of Exercise Medicine in Health and Disease

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The myogenic regulatory factor Myf5 is integral to the initiation and control of skeletal muscle formation. In adult muscle, Myf5 is expressed in satellite cells, stem cells of mature muscle, but not in the myonuclei that sustain the myofibre. Using the Myf5 nlacZ/+ mouse, we now show that Myf5 is also constitutively expressed in muscle spindles-stretch-sensitive mechanoreceptors, while muscle denervation induces extensive reactivation of the Myf5 gene in myonuclei. To identify the elements involved in the regulation of Myf5 in adult muscle, we analysed reporter gene expression in a transgenic bacterial artificial chromosome (BAC) deletion series of the Mrf4/Myf5 locus. A BAC carrying 140 kb upstream of the Myf5 transcription start site was sufficient to drive all aspects of Myf5 expression in adult muscle. In contrast, BACs carrying 88 and 59 kb upstream were unable to drive consistent expression in satellite cells, although expression in muscle spindles and reactivation of the locus in myonuclei were retained. Therefore, as during development, multiple enhancers are required to generate the full expression pattern of Myf5 in the adult. Together, these observations show that elements controlling adult Myf5 expression are genetically separable and possibly distinct from those that control Myf5 during development. These studies are a first step towards identifying cognate transcription factors involved in muscle stem cell regulation. D

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Kinetics of Myoblast Proliferation Show That Resident Satellite Cells Are Competent to Fully Regenerate Skeletal Muscle Fibers

Cited by 259 publications

References 50 publications

Insulin and Wnt1 Pathways Cooperate to Induce Reserve Cell Activation in Differentiation and Myotube Hypertrophy

Insulin and Wnt1 Pathways Cooperate to Induce Reserve Cell Activation in Differentiation and Myotube Hypertrophy

Epigenetic regulation of aging stem cells

Myogenic Regulatory Factors

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