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

doi:10.1016/j.celrep.2020.107964

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

Cell Rep. 2020 Jul 28;32(4):107964. doi: 10.1016/j.celrep.2020.107964.

Authors

Affiliations

¹ Department of Biomedical Informatics, Stanford University, Palo Alto, CA 94305, USA.
² Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
³ Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
⁴ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
⁵ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Program in Cancer Biology, University of Michigan, Ann Arbor, MI 48109, USA.
⁶ 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.
⁷ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22903, USA.
⁸ 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.
⁹ 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. Electronic address: [email protected].

Abstract

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.

Keywords: 1-carbon metabolism; Ddit3; MyoD; expression; heterochromatin; regeneration; transcription factor binding; vitamin A.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Aging / metabolism
Animals
Cell Line
Cellular Senescence / genetics*
Female
Genomics / methods
Mice
Mice, Inbred C57BL
Muscle Cells / metabolism
Muscle, Skeletal / metabolism
Myoblasts / metabolism
Regeneration / physiology
Satellite Cells, Skeletal Muscle / metabolism*
Stem Cells / metabolism*

Abstract

Publication types

MeSH terms

Grants and funding