O-GlcNAc transferase is required to maintain satellite cell function.

O-GlcNAcylation is a posttranslational modification considered to be a nutrient sensor that reports nutrient scarcity or surplus. Although O-GlcNAcylation exists in a wide range of cells and/or tissues, its functional role in muscle satellite cells (SCs) remains largely unknown. Using a genetic approach, we ablated O-GlcNAc transferase (OGT), and thus O-GlcNAcylation, in SCs. We first evaluated SC function in vivo using a muscle injury model and found that OGT deficient SCs had compromised capacity to repair muscle after an acute injury compared with the wild-type SCs. By tracing SC cycling rates in vivo using the doxycycline-inducible H2B-GFP mouse model, we found that SCs lacking OGT cycled at lower rates and reduced in abundance with time. Additionally, the self-renewal ability of OGT-deficient SCs after injury was decreased compared to that of the wild-type SCs. Moreover, in vivo, in vitro, and ex vivo proliferation assays revealed that SCs lacking OGT were incapable of expanding compared with their wild-type counterparts, a phenotype that may be explained, at least in part, by an HCF1-mediated arrest in the cell cycle. Taken together, our findings suggest that O-GlcNAcylation plays a critical role in the maintenance of SC health and function in normal and injured skeletal muscle.