Dek Modulates Global Intron Retention during Muscle Stem Cells Quiescence Exit

• DOI: 10.1016/j.devcel.2020.05.006
• Publication Date: 2020-06-04T14:56:26Z
• Authors: Lu Yue; Raymond Wan; Shaoyuan Luan; Wenshu Zeng; Tom H. Cheung
• Keywords: Oncogene Proteins; 0301 basic medicine; Satellite Cells, Skeletal Muscle; Cell Differentiation; Introns; DNA-Binding Proteins; Mice, Inbred C57BL; Mice; 03 medical and health sciences; HEK293 Cells; Animals; Humans; RNA Processing, Post-Transcriptional; Poly-ADP-Ribose Binding Proteins; Transcriptome; Cells, Cultured

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.