[20230328]SOPRESCU-Dissertation.pdf

Skeletal muscle takes up nearly 40% of total body mass, is critical for daily function by

providing balance, supports breathing, movement, and energy expenditure. Preserving

skeletal muscle can also significantly improve one’s quality by maintaining balance, movement

and improving metabolic health [1, 2]. This becomes more imperative with age, as skeletal muscle mass naturally declines, and further compounds decline in quality of life and health [1, 2]. Thus, it is critical to understand the physiology of skeletal muscle and the underlying cellular and

molecular mechanisms that contribute to normal function. Using mouse models to further our

understanding, this dissertation leverages single-cell RNA-sequencing (scRNA-seq) to dissect the

cellular and molecular underpinnings of skeletal muscle injury and repair. Specifically, chapter 1

provides an overview of skeletal muscle structure, muscle regeneration, and the current state of

scRNA-seq literature in muscle regeneration. In chapter 2, I will discuss the large-scale scRNAseq of regenerating muscle which identified dynamic population of resident and infiltrating cells. In chapter 3, I will discuss the potential immunomodulatory role of MuSCs and leveraging scRNAseq data to understand the cellular mechanisms that govern successful muscle regeneration. Finally, in chapter 4 I will discuss the role of the transcription factor Sox11, which was identified by scRNA-seq and was specific to differentiating MuSCs. Thus, this dissertation spans the cellular and molecular components of muscle regeneration.