摘要：SummaryRegulation of chromatin accessibility is critical for cell fate decisions. Chromatin structure responds to extrinsic environments rapidly. The traditional adult stem cell isolation approach requires tissue dissociation, which triggers stem cell activation and leads to alterations in chromatin structure. To preserve thein vivochromatin states, we utilized the PFA-perfusion-based isolation approach and characterized the DNA regulatory landscapes during muscle stem cell quiescence exit and aging. We showed that aged SCs display a chronically activated chromatin signature. Detailed analysis of the chromatin accessibility profiles identified key enhancer elements for SC quiescence. Constant activation of the enhancer elements promotes stemness and prevents SCs from differentiation, whereas genetic deletion causes cell-cycle arrest and leads to defects in activation. Our comprehensive characterization of the chromatin accessibility and transcriptomic landscapes in SC quiescence and aging broadens our understanding of these processes and identifies key distal regulatory elements for SC function.Graphical abstractDisplay OmittedHighlights•Performed time-course profiling ofin situfixed muscle stem cells on activation•Showed rapid changes in chromatin accessibility in muscle stem cell early activation•Identified Pax7 enhancers for muscle stem cell quiescence and activation•Aged quiescent muscle stem cells display chronically activated chromatin signatureCell biology; Stem cells research; Omics; Transcriptomics.
