Skeletal Muscle Stem Cells (MuSCs), also called Satellite Cells (SCs), are actively maintained in quiescence but can activate quickly upon extrinsic stimuli. Age-associated impairments in stem cell function correlate with the decline in somatic tissue regeneration capacity during disease or following tissue injury. However, the mechanisms of how quiescent SCs (QSCs) activate swiftly and how aging affects stem cells remains elusive. Here, we firstly identified massive proteomic changes during quiescence exit. Discordant correlation of transcriptomic and proteomic changes revealed potential translational regulation upon SC activation. Importantly, we showed CPEB1 post-transcriptionally affects protein translation during SC activation by binding to the 3’UTRs. CPEB1 phosphorylation is requ...[ Read more ]

Skeletal Muscle Stem Cells (MuSCs), also called Satellite Cells (SCs), are actively maintained in quiescence but can activate quickly upon extrinsic stimuli. Age-associated impairments in stem cell function correlate with the decline in somatic tissue regeneration capacity during disease or following tissue injury. However, the mechanisms of how quiescent SCs (QSCs) activate swiftly and how aging affects stem cells remains elusive. Here, we firstly identified massive proteomic changes during quiescence exit. Discordant correlation of transcriptomic and proteomic changes revealed potential translational regulation upon SC activation. Importantly, we showed CPEB1 post-transcriptionally affects protein translation during SC activation by binding to the 3’UTRs. CPEB1 phosphorylation is required for Myod1 protein synthesis to regulate SC activation and muscle regeneration. Also, we illustrated a pre-senescent proteomic landscape with downregulated proteins involved in transcription and translation in aged SCs. The mitochondrial proteome and activity were impaired during aging. We identified that CPEB4 is decreased in various aged tissues and regulates mitochondrial activity in SCs. CPEB4 regulates the mitochondrial proteomic landscape by binding to mitochondrial protein coding transcripts and interacts with mitochondrial translation machinery. We showed that CPEB4 regulates SC myogenic lineage progression and muscle regeneration. CPEB4 re-expression rescued impaired mitochondrial metabolism and improved aged SC function. Altogether, our study provides new angles of translational regulation of SC quiescence exit and during aging.