GLI3 regulates muscle stem cell entry into G Alert and self-renewal.

Autor: Brun CE; Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada., Sincennes MC; Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada., Lin AYT; Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada., Hall D; Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada., Jarassier W; Univ Lyon, Univ Lyon 1, CNRS, INSERM, Pathophysiology and Genetics of Neuron and Muscle, UMR5261, U1315, Institut NeuroMyoGène, 69008, Lyon, France., Feige P; Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada., Le Grand F; Univ Lyon, Univ Lyon 1, CNRS, INSERM, Pathophysiology and Genetics of Neuron and Muscle, UMR5261, U1315, Institut NeuroMyoGène, 69008, Lyon, France., Rudnicki MA; Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada. mrudnicki@ohri.ca.; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada. mrudnicki@ohri.ca.; Department of Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada. mrudnicki@ohri.ca.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Jul 08; Vol. 13 (1), pp. 3961. Date of Electronic Publication: 2022 Jul 08.
DOI: 10.1038/s41467-022-31695-5
Abstrakt: Satellite cells are required for the growth, maintenance, and regeneration of skeletal muscle. Quiescent satellite cells possess a primary cilium, a structure that regulates the processing of the GLI family of transcription factors. Here we find that GLI3 processing by the primary cilium plays a critical role for satellite cell function. GLI3 is required to maintain satellite cells in a G 0 dormant state. Strikingly, satellite cells lacking GLI3 enter the G Alert state in the absence of injury. Furthermore, GLI3 depletion stimulates expansion of the stem cell pool. As a result, satellite cells lacking GLI3 display rapid cell-cycle entry, increased proliferation and augmented self-renewal, and markedly enhanced regenerative capacity. At the molecular level, we establish that the loss of GLI3 induces mTORC1 signaling activation. Therefore, our results provide a mechanism by which GLI3 controls mTORC1 signaling, consequently regulating muscle stem cell activation and fate.
(© 2022. The Author(s).)
Databáze: MEDLINE
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