Chromatin Modifications as Determinants of Muscle Stem Cell Quiescence and Chronological Aging
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 ad...
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| Published in: | Cell reports (Cambridge) Vol. 4; no. 1; pp. 189 - 204 |
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| Main Authors: | , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
Elsevier Inc
11.07.2013
Elsevier |
| Subjects: | |
| ISSN: | 2211-1247, 2211-1247 |
| Online Access: | Get full text |
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| Abstract | 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.
[Display omitted]
•Chromatin modification pattern on myogenic regulatory factor genes in QSCs•Chromatin modification pattern on myogenic regulatory factor genes in QSCs•Increase in H3K27me3 across the genome in adult QSCs with age•Decrease of histone expression in adult QSCs with age
The comprehensive transcriptional and chromatin modification profile of an adult quiescent stem cell population, skeletal muscle satellite cells, is now examined by Rando and colleagues. The authors characterize changes associated with satellite cell activation and aging, providing direct evidence for global changes in histone modifications in adult stem cells with age. |
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| AbstractList | 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. 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. [Display omitted] •Chromatin modification pattern on myogenic regulatory factor genes in QSCs•Chromatin modification pattern on myogenic regulatory factor genes in QSCs•Increase in H3K27me3 across the genome in adult QSCs with age•Decrease of histone expression in adult QSCs with age The comprehensive transcriptional and chromatin modification profile of an adult quiescent stem cell population, skeletal muscle satellite cells, is now examined by Rando and colleagues. The authors characterize changes associated with satellite cell activation and aging, providing direct evidence for global changes in histone modifications in adult stem cells with age. 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. 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.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. |
| Author | Rando, Thomas A. Liu, Ling Leavitt, Tripp Charville, Gregory W. Shih, Johnathan Hurgo, Bernadette Marie Ceniza Cheung, Tom H. Brunet, Anne |
| AuthorAffiliation | 2 Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA 3 Neurology Service and RR&D Center of Excellence, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA 1 The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA |
| AuthorAffiliation_xml | – name: 1 The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA – name: 3 Neurology Service and RR&D Center of Excellence, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA – name: 2 Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA |
| Author_xml | – sequence: 1 givenname: Ling surname: Liu fullname: Liu, Ling organization: The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA – sequence: 2 givenname: Tom H. surname: Cheung fullname: Cheung, Tom H. organization: The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA – sequence: 3 givenname: Gregory W. surname: Charville fullname: Charville, Gregory W. organization: The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA – sequence: 4 givenname: Bernadette Marie Ceniza surname: Hurgo fullname: Hurgo, Bernadette Marie Ceniza organization: The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA – sequence: 5 givenname: Tripp surname: Leavitt fullname: Leavitt, Tripp organization: The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA – sequence: 6 givenname: Johnathan surname: Shih fullname: Shih, Johnathan organization: The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA – sequence: 7 givenname: Anne surname: Brunet fullname: Brunet, Anne organization: The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA – sequence: 8 givenname: Thomas A. surname: Rando fullname: Rando, Thomas A. email: rando@stanford.edu organization: The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23810552$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | Adult Stem Cells - cytology Adult Stem Cells - metabolism Animals Cellular Senescence Chromatin - metabolism Epigenesis, Genetic Gene Expression Regulation, Developmental Histones - genetics Histones - metabolism Methylation Mice Muscle Development Muscle Fibers, Skeletal - cytology Muscle Fibers, Skeletal - metabolism Polycomb-Group Proteins - chemistry Polycomb-Group Proteins - genetics Polycomb-Group Proteins - metabolism Protein Processing, Post-Translational Protein Structure, Tertiary Transcription Initiation Site Transcription, Genetic |
| Title | Chromatin Modifications as Determinants of Muscle Stem Cell Quiescence and Chronological Aging |
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