Intracellular inactivation of thyroid hormone is a survival mechanism for muscle stem cell proliferation and lineage progression

Monica Dentice, Raffaele Ambrosio, Valentina Damiano, Annarita Sibilio, Cristina Luongo, Ombretta Guardiola, Siham Yennek, Paola Zordan, Gabriella Minchiotti, Annamaria Colao, Alessandro Marsili, Silvia Brunelli, Luigi Del Vecchio, P. Reed Larsen, Shahragim Tajbakhsh, Domenico Salvatore

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Summary Precise control of the thyroid hormone (T3)-dependent transcriptional program is required by multiple cell systems, including muscle stem cells. Deciphering how this is achieved and how the T3 signal is controlled in stem cell niches is essentially unknown. We report that in response to proliferative stimuli such as acute skeletal muscle injury, type 3 deiodinase (D3), the thyroid hormone-inactivating enzyme, is induced in satellite cells where it reduces intracellular thyroid signaling. Satellite cell-specific genetic ablation of dio3 severely impairs skeletal muscle regeneration. This impairment is due to massive satellite cell apoptosis caused by exposure of activated satellite cells to the circulating TH. The execution of this proapoptotic program requires an intact FoxO3/MyoD axis, both genes positively regulated by intracellular TH. Thus, D3 is dynamically exploited in vivo to chronically attenuate TH signaling under basal conditions while also being available to acutely increase gene programs required for satellite cell lineage progression.

Original languageEnglish
Pages (from-to)1038-1048
Number of pages11
JournalCell Metabolism
Volume20
Issue number6
DOIs
Publication statusPublished - Dec 2 2014

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Cell Lineage
Thyroid Hormones
Muscle Cells
Stem Cells
Cell Proliferation
Skeletal Muscle
Stem Cell Niche
Iodide Peroxidase
Triiodothyronine
Genes
Regeneration
Thyroid Gland
Apoptosis
Wounds and Injuries
Enzymes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Intracellular inactivation of thyroid hormone is a survival mechanism for muscle stem cell proliferation and lineage progression. / Dentice, Monica; Ambrosio, Raffaele; Damiano, Valentina; Sibilio, Annarita; Luongo, Cristina; Guardiola, Ombretta; Yennek, Siham; Zordan, Paola; Minchiotti, Gabriella; Colao, Annamaria; Marsili, Alessandro; Brunelli, Silvia; Del Vecchio, Luigi; Larsen, P. Reed; Tajbakhsh, Shahragim; Salvatore, Domenico.

In: Cell Metabolism, Vol. 20, No. 6, 02.12.2014, p. 1038-1048.

Research output: Contribution to journalArticle

Dentice, M, Ambrosio, R, Damiano, V, Sibilio, A, Luongo, C, Guardiola, O, Yennek, S, Zordan, P, Minchiotti, G, Colao, A, Marsili, A, Brunelli, S, Del Vecchio, L, Larsen, PR, Tajbakhsh, S & Salvatore, D 2014, 'Intracellular inactivation of thyroid hormone is a survival mechanism for muscle stem cell proliferation and lineage progression', Cell Metabolism, vol. 20, no. 6, pp. 1038-1048. https://doi.org/10.1016/j.cmet.2014.10.009
Dentice, Monica ; Ambrosio, Raffaele ; Damiano, Valentina ; Sibilio, Annarita ; Luongo, Cristina ; Guardiola, Ombretta ; Yennek, Siham ; Zordan, Paola ; Minchiotti, Gabriella ; Colao, Annamaria ; Marsili, Alessandro ; Brunelli, Silvia ; Del Vecchio, Luigi ; Larsen, P. Reed ; Tajbakhsh, Shahragim ; Salvatore, Domenico. / Intracellular inactivation of thyroid hormone is a survival mechanism for muscle stem cell proliferation and lineage progression. In: Cell Metabolism. 2014 ; Vol. 20, No. 6. pp. 1038-1048.
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