
Estradiol deficiency reduces the satellite cell pool by impairing cell cycle progression
Author(s) -
Alexie A. Larson,
Ahmed S. Shams,
Shawna McMillin,
B. Patrick Sullivan,
Cha Vue,
Zachery A Roloff,
Eric Batchelor,
Michael Kyba,
Dawn A. Lowe
Publication year - 2022
Publication title -
american journal of physiology. cell physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.432
H-Index - 181
eISSN - 1522-1563
pISSN - 0363-6143
DOI - 10.1152/ajpcell.00429.2021
Subject(s) - satellite , cell cycle , cell , cell growth , biology , cell division , microbiology and biotechnology , in vivo , endocrinology , medicine , genetics , engineering , aerospace engineering
The size of the satellite cell pool is reduced in estradiol (E2)-deficient female mice and humans. Here, we use a combination of in vivo and in vitro approaches to identify mechanisms whereby E2 deficiency impairs satellite cell maintenance. By measuring satellite cell numbers in mice at several early time points post-ovariectomy (Ovx), we determine that satellite cell numbers decline by 33% between 10 and 14 days post-Ovx in tibialis anterior and gastrocnemius muscles. At 14 days post-Ovx, we demonstrate that satellite cells have a reduced propensity to transition from G0/G1 to S and G2/M phases, compared to cells from ovary-intact mice, associated with changes in two key satellite cell cycle regulators, ccna2 and p16INK4a. Further, freshly isolated satellite cells treated with E2 in vitro have 62% greater cell proliferation and require less time to complete the first division. Using clonal and differentiation assays, we measured 69% larger satellite cell colonies and enhanced satellite cell-derived myoblast differentiation with E2 treatment compared to vehicle-treated cells. Together, these results identify a novel mechanism for preservation of the satellite cell pool by E2 via promotion of satellite cell cycling.