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Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging.

Publication ,  Journal Article
Larouche, JA; Mohiuddin, M; Choi, JJ; Ulintz, PJ; Fraczek, P; Sabin, K; Pitchiaya, S; Kurpiers, SJ; Castor-Macias, J; Liu, W; Hastings, RL ...
Published in: Elife
July 29, 2021

During aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume and function impacting mobility and quality of life. Muscle loss is often associated with denervation and a loss of resident muscle stem cells (satellite cells or MuSCs); however, the relationship between MuSCs and innervation has not been established. Herein, we administered severe neuromuscular trauma to a transgenic murine model that permits MuSC lineage tracing. We show that a subset of MuSCs specifically engraft in a position proximal to the neuromuscular junction (NMJ), the synapse between myofibers and motor neurons, in healthy young adult muscles. In aging and in a mouse model of neuromuscular degeneration (Cu/Zn superoxide dismutase knockout - Sod1-/-), this localized engraftment behavior was reduced. Genetic rescue of motor neurons in Sod1-/- mice reestablished integrity of the NMJ in a manner akin to young muscle and partially restored MuSC ability to engraft into positions proximal to the NMJ. Using single cell RNA-sequencing of MuSCs isolated from aged muscle, we demonstrate that a subset of MuSCs are molecularly distinguishable from MuSCs responding to myofiber injury and share similarity to synaptic myonuclei. Collectively, these data reveal unique features of MuSCs that respond to synaptic perturbations caused by aging and other stressors.

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Published In

Elife

DOI

EISSN

2050-084X

Publication Date

July 29, 2021

Volume

10

Location

England

Related Subject Headings

  • Superoxide Dismutase-1
  • Neuromuscular Junction
  • Myoblasts, Skeletal
  • Muscle, Skeletal
  • Mice, Knockout
  • Mice
  • Male
  • Female
  • Animals
  • Aging
 

Citation

APA
Chicago
ICMJE
MLA
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Larouche, J. A., Mohiuddin, M., Choi, J. J., Ulintz, P. J., Fraczek, P., Sabin, K., … Aguilar, C. A. (2021). Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging. Elife, 10. https://doi.org/10.7554/eLife.66749
Larouche, Jacqueline A., Mahir Mohiuddin, Jeongmoon J. Choi, Peter J. Ulintz, Paula Fraczek, Kaitlyn Sabin, Sethuramasundaram Pitchiaya, et al. “Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging.Elife 10 (July 29, 2021). https://doi.org/10.7554/eLife.66749.
Larouche JA, Mohiuddin M, Choi JJ, Ulintz PJ, Fraczek P, Sabin K, et al. Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging. Elife. 2021 Jul 29;10.
Larouche, Jacqueline A., et al. “Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging.Elife, vol. 10, July 2021. Pubmed, doi:10.7554/eLife.66749.
Larouche JA, Mohiuddin M, Choi JJ, Ulintz PJ, Fraczek P, Sabin K, Pitchiaya S, Kurpiers SJ, Castor-Macias J, Liu W, Hastings RL, Brown LA, Markworth JF, De Silva K, Levi B, Merajver SD, Valdez G, Chakkalakal JV, Jang YC, Brooks SV, Aguilar CA. Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging. Elife. 2021 Jul 29;10.

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

July 29, 2021

Volume

10

Location

England

Related Subject Headings

  • Superoxide Dismutase-1
  • Neuromuscular Junction
  • Myoblasts, Skeletal
  • Muscle, Skeletal
  • Mice, Knockout
  • Mice
  • Male
  • Female
  • Animals
  • Aging