Myonuclear domain flexibility challenges rigid assumptions on satellite cell contribution to skeletal muscle fiber hypertrophy

Kevin A. Murach, Davis A. Englund, Esther E. Dupont-Versteegden, John J. McCarthy, Charlotte A. Peterson

Research output: Contribution to journalShort surveypeer-review

59 Scopus citations


Satellite cell-mediated myonuclear accretion is thought to be required for skeletal muscle fiber hypertrophy, and even drive hypertrophy by preceding growth. Recent studies in humans and rodents provide evidence that challenge this axiom. Specifically, Type 2 muscle fibers reliably demonstrate a substantial capacity to hypertrophy in the absence of myonuclear accretion, challenging the notion of a tightly regulated myonuclear domain (i.e., area that each myonucleus transcriptionally governs). In fact, a "myonuclear domain ceiling", or upper limit of transcriptional output per nucleus to support hypertrophy, has yet to be identified. Satellite cells respond to muscle damage, and also play an important role in extracellular matrix remodeling during loading-induced hypertrophy. We postulate that robust satellite cell activation and proliferation in response to mechanical loading is largely for these purposes. Future work will aim to elucidate the mechanisms by which Type 2 fibers can hypertrophy without additional myonuclei, the extent to which Type 1 fibers can grow without myonuclear accretion, and whether a true myonuclear domain ceiling exists.

Original languageEnglish
Article number635
JournalFrontiers in Physiology
Issue numberMAY
StatePublished - May 29 2018

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grants AR071753 (to KM), AR60701 and AG049806, (to CP and JM), and AT009268 (ED-V).

Publisher Copyright:
© 2018 Murach, Englund, Dupont-Versteegden, McCarthy and Peterson.


  • Muscle damage
  • Muscle regeneration
  • Myonuclei
  • Pax7-DTA
  • Type 2 fibers

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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