Dissecting Murine Muscle Stem Cell Aging through Regeneration Using Integrative Genomic Analysis

被引:45
作者
Shcherbina, Anna [1 ]
Larouche, Jacqueline [2 ,3 ]
Fraczek, Paula [2 ,3 ]
Yang, Benjamin A. [2 ,3 ]
Brown, Lemuel A. [4 ]
Markworth, James F. [4 ]
Chung, Carolina H. [2 ]
Khaliq, Mehwish [2 ,5 ]
de Silva, Kanishka [2 ,3 ]
Choi, Jeongmoon J. [7 ,8 ,9 ]
Fallahi-Sichani, Mohammad [2 ,10 ]
Chandrasekaran, Sriram [2 ]
Jang, Young C. [7 ,8 ,9 ]
Brooks, Susan, V [2 ,4 ]
Aguilar, Carlos A. [2 ,3 ,6 ]
机构
[1] Stanford Univ, Dept Biomed Informat, Palo Alto, CA 94305 USA
[2] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Biointerfaces Inst, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA
[5] Univ Michigan, Program Canc Biol, Ann Arbor, MI 48109 USA
[6] Univ Michigan, Program Cellular & Mol Biol, Ann Arbor, MI 48109 USA
[7] Georgia Inst Technol, Parker H Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA
[8] Georgia Inst Technol, Sch Biol Sci, Atlanta, GA 30332 USA
[9] Georgia Inst Technol, Wallace Coulter Dept Biomed Engn, Atlanta, GA 30332 USA
[10] Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22903 USA
来源
CELL REPORTS | 2020年 / 32卷 / 04期
基金
美国国家卫生研究院;
关键词
SKELETAL-MUSCLE; PROGENITOR CELLS; SATELLITE CELLS; SELF-RENEWAL; CHROMATIN; QUIESCENCE; BINDING; SWITCH; FATE; ARCHITECTURE;
D O I
10.1016/j.celrep.2020.107964
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
During aging, there is a progressive loss of volume and function in skeletal muscle that impacts mobility and quality of life. The repair of skeletal muscle is regulated by tissue-resident stem cells called satellite cells (or muscle stem cells [MuSCs]), but in aging, MuSCs decrease in numbers and regenerative capacity. The transcriptional networks and epigenetic changes that confer diminished regenerative function in MuSCs as a result of natural aging are only partially understood. Herein, we use an integrative genomics approach to profile MuSCs from young and aged animals before and after injury. Integration of these datasets reveals aging impacts multiple regulatory changes through significant differences in gene expression, metabolic flux, chromatin accessibility, and patterns of transcription factor (TF) binding activities. Collectively, these datasets facilitate a deeper understanding of the regulation tissue-resident stem cells use during aging and healing.
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页数:24
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