Browsing by Subject "muscle stem cells"

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    Satellite cell maintenance and strength recovery after injury: the impact of estradiol signaling
    (2021-12) Larson, Alexie
    My dissertation work established a crucial role for estradiol (E2) in the recovery of muscle strength after injuries and maintenance of the satellite cell population under homeostatic conditions (Chapters 3 & 4). I demonstrated that E2 deficiency impairs the adaptive potential of skeletal muscle after repeated injuries, indicated by blunted muscle mass and strength, and that the reduction in satellite cell number with E2 deficiency likely contributes to this impairment (Chapter 3). With the ovariectomy mouse model and a transgenic female mouse model that specifically ablated ER⍺ in satellite cells, I demonstrated that E2 is the hormone that drives the loss of satellite cells as opposed to any other ovarian hormone, and that the loss of E2 or its receptor for only 14 d impairs satellite cell maintenance (Chapter 4). Mechanistically, I showed that impaired satellite cell maintenance caused by E2 deficiency involves altered satellite cell cycle progression, kinetics, proliferation, and differentiation (Chapter 4). The work of my dissertation highlights a novel mechanism for E2 in maintaining the satellite cell population in female mice through appropriate satellite cell cycle progression. My findings, accompanied by future studies that identify E2-sensitive molecular pathways in satellite cells, are instrumental for developing effective therapies to preserve efficient skeletal muscle regeneration and improve overall skeletal muscle health of post-menopausal women.