Dek Modulates Global Intron Retention to Control Quiescence Exit in Muscle Stem Cells

Quiescent adult stem cells have the ability to respond rapidly to external stimuli, but mechanisms of such rapid activation remain elusive. Using quiescent skeletal muscle stem cells (QSCs), we showed that intron retention (IR) is prevalent. Genes possessing IR are essential for various fundamental cellular functions including RNA splicing, protein translation, cell cycle entry and lineage specification. Further analysis revealed that IR is a post-transcriptional mechanism that regulates QSC quiescence exit, which is dependent on the phosphorylated-Dek protein. While Dek is absent in QSCs, overexpression of Dek in QSC in vivo results in a global decrease of IR, quiescence exit, and consequently undermine muscle regeneration. Moreover, IR analysis on public RNA-seq data shows that other quiescent adult stem cells are enriched with retained introns, indicating IR as a feature of quiescent adult stem cells. Altogether, these findings suggest that intron retention plays an important role in stem cell quiescence exit.