Myostatin regulates tissue potency and cardiac calcium-handling proteins.

Attenuating myostatin enhances striated muscle growth, reduces adiposity, and improves cardiac contractility. To determine whether myostatin influences tissue potency in a manner that could control such pleiotropic actions, we generated label-retaining mice with wild-type and mstn(-/-) (Jekyll) backgrounds in which slow-cycling stem, transit-amplifying, and progenitor cells are preferentially labeled by histone 2B/green fluorescent protein. Jekyll mice were born with fewer label-retaining cells (LRCs) in muscle and heart, consistent with increased stem/progenitor cell contributions to embryonic growth of both tissues. Cardiac LRC recruitment from noncardiac sources occurred in both groups, but lasted longer in Jekyll hearts, whereas heightened beta-adrenergic sensitivity of mstn(-/-) hearts was explained by elevated SERCA2a, phospholamban, and beta 2-adrenergic receptor levels. Jekyll mice were also born with more adipose LRCs despite significantly smaller tissue weights. Reduced adiposity in mstn(-/-) animals is therefore due to reduced lipid deposition as adipoprogenitor pools appear to be enhanced. By contrast, increased bone densities of mstn(-/-) mice are likely compensatory to hypermuscularity because LRC counts were similar in Jekyll and wild-type tibia. Myostatin therefore significantly influences the potency of different tissues, not just muscle, as well as cardiac Ca2+-handling proteins. Thus, the pleiotropic phenotype of mstn(-/-) animals may not be due to enhanced muscle development per se, but also to altered stem/progenitor cell pools that ultimately influence tissue potency.