p110α of PI3K is Indispensable for Quiescence Exit in Adult Muscle Satellite Cells. p110α of PI3K is Indispensable for Quiescence Exit in Adult Muscle Satellite Cells

Adult muscle stem cells (MuSC) are quiescent with a localization between myofibers and basal lamina. Upon injury, MuSC exit quiescence, reenter cell cycle, expand and differentiate for muscle regeneration. By using genetic mouse model, we identified p110α/mTORC1 signaling as a indispensable pathway that permits quiescence exit and cell cycle reentry. In order to dig out the downstream effectors, we compared the transcriptome of freshly isolated MuSC from Ctrl (p110α-f/+:R26-YFP/YFP:Pax7-CreER/CreER) to MuSC-specific p110α-null (iKO, p110α-f/f:R26-YFP/YFP:Pax7-CreER/CreER) mice by RNA-sequencing, and AP1 target genes were dramatically down-regulated in iKO MuSC. Restoration of Jun could significantly rescue the cell cycle reentry defect in iKO MuSC. In summary, we provided a p110α/mTORC1/Jun axis required for quiecence exit and cell cycle reentry of MuSC. Overall design: 2-month-old Ctrl and iKO mice (n=4 in each group) were injected with 5 consecutive doses of Tamoxifen (Tmx) followed by 7 doses of Tmx every 2-3 days. Total RNAs were extracted from freshly isolated MuSC from Ctrl and iKO mice and subjected to gene expression profiling.