Dissecting Murine Muscle Stem Cell Aging through Regeneration Using Integrative Genomic Analysis
Anna Shcherbina,
Jacqueline Larouche,
Paula Fraczek,
Benjamin A. Yang,
Lemuel A. Brown,
James F. Markworth,
Carolina H. Chung,
Mehwish Khaliq,
Kanishka de Silva,
Jeongmoon J. Choi,
Mohammad Fallahi-Sichani,
Sriram Chandrasekaran,
Young C. Jang,
Susan V. Brooks,
Carlos A. Aguilar
Affiliations
Anna Shcherbina
Department of Biomedical Informatics, Stanford University, Palo Alto, CA 94305, USA
Jacqueline Larouche
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA
Paula Fraczek
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA
Benjamin A. Yang
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA
Lemuel A. Brown
Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
James F. Markworth
Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
Carolina H. Chung
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
Mehwish Khaliq
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Program in Cancer Biology, University of Michigan, Ann Arbor, MI 48109, USA
Kanishka de Silva
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA
Jeongmoon J. Choi
Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA; Wallace Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
Mohammad Fallahi-Sichani
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22903, USA
Sriram Chandrasekaran
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
Young C. Jang
Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA; Wallace Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
Susan V. Brooks
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
Carlos A. Aguilar
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA; Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI 48109, USA; Corresponding author
Summary: 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.
