GLI3 regulates muscle stem cell entry into G<sub>Alert</sub> and self-renewal.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35803939.
- Also identified by DOI 10.1038/s41467-022-31695-5 and PMC identifier 9270324.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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<sub>0</sub> dormant state. Strikingly, satellite cells lacking GLI3 enter the G<sub>Alert</sub> 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.
Medical subject headings
- Satellite Cells, Skeletal Muscle