Dek Modulates Global Intron Retention during Muscle Stem Cells Quiescence Exit.

Adult stem cells are essential for tissue regeneration. However, the mechanisms underlying the activation of quiescent adult stem cells remain elusive. Using skeletal muscle stem cells, also called satellite cells (SCs), we demonstrate prevalent intron retention (IR) in the transcriptome of quiescent SCs (QSCs). Intron-retained transcripts found in QSCs are essential for fundamental functions including RNA splicing, protein translation, cell-cycle entry, and lineage specification. Further analysis reveals that phosphorylated Dek protein modulates IR during SC quiescence exit. While Dek protein is absent in QSCs, Dek overexpression in vivo results in a global decrease of IR, quiescence dysregulation, premature differentiation of QSCs, and undermined muscle regeneration. Moreover, IR analysis on hundreds of public RNA-seq data show that IR is conserved among quiescent adult stem cells. Altogether, we illustrate IR as a conserved post-transcriptional regulation mechanism that plays an important role during stem cell quiescence exit. • Quiescent muscle stem cells possess widespread intron retention • Dek regulates intron removal during muscle stem cell activation • Dek overexpression promotes intron removal and disrupts quiescence • Intron retention is a common feature among quiescent adult stem cells Yue et al. revealed prevalent intron retention in quiescent muscle stem cells. Dek mediates intron removal during the quiescence exit of muscle stem cells and promotes muscle stem cell activation. Intron retention is a common feature among quiescent adult stem cells. [ABSTRACT FROM AUTHOR]