p110α of PI3K is necessary and sufficient for quiescence exit in adult muscle satellite cells.
EMBO J
; 37(8)2018 04 13.
Article
en En
| MEDLINE
| ID: mdl-29581096
ABSTRACT
Adult mouse muscle satellite cells (MuSCs) are quiescent in uninjured muscles. Upon injury, MuSCs exit quiescence in vivo to become activated, re-enter the cell cycle to proliferate, and differentiate to repair the damaged muscles. It remains unclear which extrinsic cues and intrinsic signaling pathways regulate quiescence exit during MuSC activation. Here, we demonstrated that inducible MuSC-specific deletion of p110α, a catalytic subunit of phosphatidylinositol 3-kinase (PI3K), rendered MuSCs unable to exit quiescence, resulting in severely impaired MuSC proliferation and muscle regeneration. Genetic reactivation of mTORC1, or knockdown of FoxOs, in p110α-null MuSCs partially rescued the above defects, making them key effectors downstream of PI3K in regulating quiescence exit. c-Jun was found to be a key transcriptional target of the PI3K/mTORC1 signaling axis essential for MuSC quiescence exit. Moreover, induction of a constitutively active PI3K in quiescent MuSCs resulted in spontaneous MuSC activation in uninjured muscles and subsequent depletion of the MuSC pool. Thus, PI3K-p110α is both necessary and sufficient for MuSCs to exit quiescence in response to activating signals.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Células Satélite del Músculo Esquelético
/
Fosfatidilinositol 3-Quinasa Clase I
Límite:
Animals
Idioma:
En
Revista:
EMBO J
Año:
2018
Tipo del documento:
Article
País de afiliación:
China