O ‐GlcNAc transferase is required to maintain satellite cell function

O ‐GlcNAcylation is a widespread nutrient sensitive post‐translational modification that satellite cells (SCs) use to maintain homeostasis and proper SC function. Ablation of SC specific OGT impairs adult regenerative myogenesis,in vivo cycling properties, and proliferation, presumably through an HCF1 ‐mediated arrest in the cell cycle. AbstractO ‐GlcNAcylation is a post‐translational 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 geneti c approach, we ablated O‐GlcNAc transferase (OGT), and thus O‐GlcNAcylation, in SCs. We first evaluated SC functionin vivo using a muscle injury model and found that OGT deficient SCs had compromised capacity to repair muscle after an acute injury compared to the wild ‐type SCs. By tracing SC cycling ratesin 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, andex vivo proliferation assays revealed that SCs lacking OGT were incapable of expanding compared to their wild ‐type counterparts, a phenotype that may be explained, at least in part, by an HCF1‐mediated arrest ...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Tissue ‐Specific Stem Cells Source Type: research