The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell Rep. 2013 Jul 11;4(1):189-204. doi: 10.1016/j.celrep.2013.05.043. Epub 2013 Jun 27.
The ability to maintain quiescence is critical for the long-term maintenance of a functional stem cell pool. To date, the epigenetic and transcriptional characteristics of quiescent stem cells and how they change with age remain largely unknown. In this study, we explore the chromatin features of adult skeletal muscle stem cells, or satellite cells (SCs), which reside predominantly in a quiescent state in fully developed limb muscles of both young and aged mice. Using a ChIP-seq approach to obtain global epigenetic profiles of quiescent SCs (QSCs), we show that QSCs possess a permissive chromatin state in which few genes are epigenetically repressed by Polycomb group (PcG)-mediated histone 3 lysine 27 trimethylation (H3K27me3), and a large number of genes encoding regulators that specify nonmyogenic lineages are demarcated by bivalent domains at their transcription start sites (TSSs). By comparing epigenetic profiles of QSCs from young and old mice, we also provide direct evidence that, with age, epigenetic changes accumulate and may lead to a functional decline in quiescent stem cells. These findings highlight the importance of chromatin mapping in understanding unique features of stem cell identity and stem cell aging.
维持静止状态的能力对于功能性干细胞池的长期维持至关重要。迄今为止，静止干细胞的表观遗传学和转录特征以及它们随年龄的变化在很大程度上仍然未知。在这项研究中，我们探讨了成年骨骼肌干细胞或卫星细胞 (SCs) 的染色质特征，这些细胞在年轻和老年小鼠完全发育的肢体肌肉中主要处于静止状态。我们使用 ChIP-seq 方法获得静止 SC（QSC）的全局表观遗传图谱，结果表明 QSC 具有允许的染色质状态，其中很少有基因被 Polycomb 组 (PcG)-介导的组蛋白 3 赖氨酸 27 三甲基化 (H3K27me3) 表观遗传抑制，并且大量编码指定非肌源性谱系的基因在其转录起始位点 (TSS) 处被双价结构域标记。通过比较年轻和老年小鼠 QSC 的表观遗传图谱，我们还提供了直接证据，表明随着年龄的增长，表观遗传变化会累积，并可能导致静止干细胞的功能下降。这些发现强调了染色质图谱在理解干细胞特性和干细胞衰老的独特特征方面的重要性。
