Chromatin Modifications as Determinants of Muscle Stem Cell Quiescence and Chronological Aging
Ling Liu,
Tom H. Cheung,
Gregory W. Charville,
Bernadette Marie Ceniza Hurgo,
Tripp Leavitt,
Johnathan Shih,
Anne Brunet,
Thomas A. Rando
Affiliations
Ling Liu
The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA
Tom H. Cheung
The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA
Gregory W. Charville
The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA
Bernadette Marie Ceniza Hurgo
The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA
Tripp Leavitt
The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA
Johnathan Shih
The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA
Anne Brunet
The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA
Thomas A. Rando
The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA
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.
