GLI3 regulates muscle stem cell entry into GAlert and self-renewal
© 2022. The Author(s)..
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 G0 dormant state. Strikingly, satellite cells lacking GLI3 enter the GAlert 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
|---|---|
| Enthalten in: |
Nature communications - 13(2022), 1 vom: 08. Juli, Seite 3961 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Brun, Caroline E [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
EC 2.7.11.1 |
|---|
| Anmerkungen: |
Date Completed 12.07.2022 Date Revised 17.08.2022 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41467-022-31695-5 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM343244543 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM343244543 | ||
| 003 | DE-627 | ||
| 005 | 20231226020000.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-022-31695-5 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1144.xml |
| 035 | |a (DE-627)NLM343244543 | ||
| 035 | |a (NLM)35803939 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Brun, Caroline E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a GLI3 regulates muscle stem cell entry into GAlert and self-renewal |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 12.07.2022 | ||
| 500 | |a Date Revised 17.08.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a 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 G0 dormant state. Strikingly, satellite cells lacking GLI3 enter the GAlert 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Mechanistic Target of Rapamycin Complex 1 |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 700 | 1 | |a Sincennes, Marie-Claude |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Alexander Y T |e verfasserin |4 aut | |
| 700 | 1 | |a Hall, Derek |e verfasserin |4 aut | |
| 700 | 1 | |a Jarassier, William |e verfasserin |4 aut | |
| 700 | 1 | |a Feige, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Le Grand, Fabien |e verfasserin |4 aut | |
| 700 | 1 | |a Rudnicki, Michael A |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 13(2022), 1 vom: 08. Juli, Seite 3961 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
| 773 | 1 | 8 | |g volume:13 |g year:2022 |g number:1 |g day:08 |g month:07 |g pages:3961 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-022-31695-5 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 13 |j 2022 |e 1 |b 08 |c 07 |h 3961 | ||