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.

成人干细胞对于组织再生至关重要。但是，静止的成年干细胞活化的潜在机制仍然难以捉摸。使用骨骼肌干细胞，也称为卫星细胞（SCs），我们证明了静态SCs（QSCs）转录组中普遍存在的内含子保留（IR）。在QSC中发现的内含子保留的转录本对于基本功能至关重要，包括RNA剪接，蛋白质翻译，细胞周期进入和谱系规格。进一步的分析表明，磷酸化的Dek蛋白可在SC静止退出时调节IR。QSC中不存在Dek蛋白，而在体内Dek过表达导致IR的整体下降，静态失调，QSC的过早分化以及破坏的肌肉再生。此外，对数百种公共RNA-seq数据进行的IR分析表明，IR在成年干细胞中是保守的。总之，我们将IR示为一种保守的转录后调控机制，该机制在干细胞静止退出过程中起着重要作用。