Estradiol deficiency reduces the satellite cell pool by impairing cell cycle progression

Alexie A. Larson, Ahmed S. Shams, Shawna L. McMillin, Brian P. Sullivan, Cha Vue, Zachery A. Roloff, Eric Batchelor, Michael Kyba, Dawn A Lowe

Research output: Contribution to journalArticlepeer-review

Abstract

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 postovariectomy (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 with 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 with 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.

Original languageEnglish (US)
Pages (from-to)C1123-C1137
JournalAmerican journal of physiology. Cell physiology
Volume322
Issue number6
DOIs
StatePublished - Jun 1 2022

Bibliographical note

Funding Information:
This study was funded by the National Institute of Health (NIH) Grants R01-AG062899 (D.A.L. and M.K.) and R01-AG031743 (D.A. L.). A.A.L. was supported on T32-AG029796 and S.L.M. was supported on T32-AR007612.

Publisher Copyright:
© 2022 American Physiological Society. All rights reserved.

Keywords

  • muscle stem cells
  • ovariectomy
  • satellite cell cycling
  • skeletal muscle

PubMed: MeSH publication types

  • Journal Article

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