Thyroid hormone signaling and deiodinase actions in muscle stem/progenitor cells

Thyroid hormone (TH) regulates such crucial biological functions as normal growth, development and metabolism of nearly all vertebrate tissues. In skeletal muscle, TH plays a critical role in regulating the function of satellite cells, the bona fide skeletal muscle stem cells. Deiodinases (D2 and D3) have been found to modulate the expression of various TH target genes in satellite cells. Regulation of the expression and activity of the deiodinases constitutes a cell-autonomous, pre-receptor mechanism that controls crucial steps during the various phases of myogenesis. Here, we review the roles of deiodinases in skeletal muscle stem cells, particularly in muscle homeostasis and upon regeneration. We focus on the role of T3 in stem cell functions and in commitment towards lineage progression. We also discuss how deiodinases might be therapeutically exploited to improve satellite-cell-mediated muscle repair in skeletal muscle disorders or injury. The relationship between muscle regeneration, thyroid hormones and deiodinases. Differential expression of D2 and D3 alters the active thyroid hormone concentration (T3) that regulates critical factors in the lineage progression and differentiation of muscle stem cells. The role and activity of the deiodinases in the quiescent state of muscle stem cells remains to be established. The genes directly regulated by thyroid hormone are shown in red. MHC: myosin heavy chain. [Display omitted] •Muscle stem cells are highly sensitive to thyroid hormone levels.•Type 2 and Type 3 deiodinase are expressed and finely tuned in muscle stem cells.•Concerted deiodinase activities dynamically regulate local T3 availability in muscle stem cells.