Myostatin negatively regulates satellite cell activation and self-renewal

By Seumas McCroskery, Mark Thomas, L. Maxwell, Mridula Sharma, R. Kambadur. Journal of Cell Biology, 2003

837 citations recorded by the source corpus.

Satellite cells are quiescent muscle stem cells that promote postnatal muscle growth and repair. Here we show that myostatin, a TGF-β member, signals satellite cell quiescence and also negatively regulates satellite cell self-renewal. BrdU labeling in vivo revealed that, among the Myostatin-deficient satellite cells, higher numbers of satellite cells are activated as compared with wild type. In contrast, addition of Myostatin to myofiber explant cultures inhibits satellite cell activation. Cell cycle analysis confirms that Myostatin up-regulated p21, a Cdk inhibitor, and decreased the levels and activity of Cdk2 protein in satellite cells. Hence, Myostatin negatively regulates the G1 to S progression and thus maintains the quiescent status of satellite cells. Immunohistochemical analysis with CD34 antibodies indicates that there is an increased number of satellite cells per unit length of freshly isolated Mstn−/− muscle fibers. Determination of proliferation rate suggests that this elevation in satellite cell number could be due to increased self-renewal and delayed expression of the differentiation gene (myogenin) in Mstn−/− adult myoblasts. Taken together, these results suggest that Myostatin is a potent negative regulator of satellite cell activation and thus signals the quiescence of satellite cells.

Subfields: Genetics, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/ad2396f5dde5b0a46a84d7ce5dbc3800fc512618

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In Genetics

1. J. Hawley
2. A. Goldberg
3. Vernon G. Coffey

In Molecular Biology

1. J. Hawley
2. A. Goldberg
3. D. Lacey
4. W. S. Simonet
5. Vernon G. Coffey
6. M. Sandri

Citations in the corpus

• Sarcopenia: etiology, clinical consequences, intervention, and assessment (2009, background): “Another factor in the behavior of muscle satellite cells is myostatin, which is thought to suppress differentiation and proliferation of myocytes by suppressing the expression of MRFs such as myoD and myogenin [53].”
• The Molecular Bases of Training Adaptation (2007, background): “Myostatin appears to exert its regulatory effect on muscle mass via inhibition of satellite cell proliferation, differentiation and self-renewal (Thomas et al. 2000; Langley et al. 2002; McCroskery et al. 2003).”
• Enhancement of meat production by environmental manipulations in embryo and young broilers (2006, background): “…cell proliferation and differentiation (Thomas et al., 2000; Joulia et al., 2003) by World’s Poultry Science Journal, Vol. 62, September 2006 489 maintaining them in their quiescent state (McCroskery et al., 2003) and by downregulating the expression of MyoD family members (Langley et al., 2002).”
• Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival. (2010, background): “Genetic ablation of myostatin has been reported to cause satellite cell activation (McCroskery et al., 2003).”