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

• Published in: Cell reports (Cambridge) Vol. 32; no. 4; p. 107964
• Main Authors: Shcherbina, Anna, Larouche, Jacqueline, Fraczek, Paula, Yang, Benjamin A., Brown, Lemuel A., Markworth, James F., Chung, Carolina H., Khaliq, Mehwish, de Silva, Kanishka, Choi, Jeongmoon J., Fallahi-Sichani, Mohammad, Chandrasekaran, Sriram, Jang, Young C., Brooks, Susan V., Aguilar, Carlos A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.07.2020; Elsevier
• Subjects: 1-carbon metabolism; Aging - metabolism; Animals; Cell Line; Cellular Senescence - genetics; Ddit3; expression; Female; Genomics - methods; heterochromatin; Mice; Mice, Inbred C57BL; Muscle Cells - metabolism; Muscle, Skeletal - metabolism; Myoblasts - metabolism; MyoD; regeneration; Regeneration - physiology; Satellite Cells, Skeletal Muscle - metabolism; Stem Cells - metabolism; transcription factor binding; vitamin A; 1-carbon metabolism; expression; vitamin A; regeneration; MyoD; Ddit3; transcription factor binding; heterochromatin
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.107964

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. [Display omitted] •Chromatin enzymes that mediate heterochromatin packaging vary in aging•Distinct activity of one-carbon and retinol pathways observed in aged satellite cells•Changes in transcription factor binding in aged satellite cells post-injury The number and regenerative capacity of tissue-resident stem muscle cells are attenuated with age. Shcherbina et al. profile MuSCs from young and aged animals pre- and post-injury, discovering that aging impacts regulatory changes through differences in gene expression, metabolic flux, chromatin accessibility, and transcription factor binding.