GSE109472
p110a 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 p110a/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 (p110a-f/+:R26-YFP/YFP:Pax7-CreER/CreER) to MuSC-specific p110a-null (iKO, p110a-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 p110a/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.