Thyroid Hormone Transporters MCT8 and OATP1C1 Control Skeletal Muscle Regeneration

Publication date: Available online 26 April 2018 Source:Stem Cell Reports Author(s): Steffen Mayerl, Manuel Schmidt, Denica Doycheva, Veerle M. Darras, Sören S. Hüttner, Anita Boelen, Theo J. Visser, Christoph Kaether, Heike Heuer, Julia von Maltzahn Thyroid hormone (TH) transporters are required for the transmembrane passage of TH in target cells. In humans, inactivating mutations in the TH transporter MCT8 cause the Allan-Herndon-Dudley syndrome, characterized by severe neuromuscular symptoms and an abnormal TH serum profile, which is fully replicated in Mct8 knockout mice and Mct8/Oatp1c1 double-knockout (M/O DKO) mice. Analysis of tissue TH content and expression of TH-regulated genes indicate a thyrotoxic state in Mct8-deficient skeletal muscles. Both TH transporters are upregulated in activated satellite cells (SCs). In M/O DKO mice, we observed a strongly reduced number of differentiated SCs, suggesting an impaired stem cell function. Moreover, M/O DKO mice and mice lacking both transporters exclusively in SCs showed impaired skeletal muscle regeneration. Our data provide solid evidence for a unique gate-keeper function of MCT8 and OATP1C1 in SC activation, underscoring the importance of a finely tuned TH signaling during myogenesis. Teaser In this article, Mayerl and colleagues demonstrate that the thyroid hormone transporters MCT8 and OATP1C1 are unique gate-keepers in activated muscle stem cells. The expression of both transporters increases upon acti...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research