@article{a4d1084d44e04ac6986440c066fd7940,
title = "Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging",
abstract = "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.",
author = "Larouche, {Jacqueline A.} and Mahir Mohiuddin and Choi, {Jeongmoon J.} and Ulintz, {Peter J.} and Paula Fraczek and Kaitlyn Sabin and Sethuramasundaram Pitchiaya and Kurpiers, {Sarah J.} and Jesus Castor-Macias and Wenxuan Liu and Hastings, {Robert Louis} and Brown, {Lemuel A.} and Markworth, {James F.} and {de Silva}, Kanishka and Levi, {Benjamin D.} and Merajver, {Sofia D.} and Gregorio Valdez and Chakkalakal, {Joe V.} and Jang, {Young C.} and Brooks, {Susan V.} and Aguilar, {Carlos A.}",
note = "Funding Information: Research reported in this publication was partially supported by National Institute on Arthritis and Musculoskeletal Disease of the National Institutes of Health under Award Number P30 AR069620 (CAA, SVB) and R01 AR071379 (BDL), R61 AR078072 (BDL), the National Institute on Aging P01 AG051442 (SVB), the National Institute on Aging R01 AG051456 (JVC), the Breast Cancer Research Foundation (PJU, SDM), the 3M Foundation (CAA), American Federation for Aging Research Grant for Junior Faculty (CAA), the University of Michigan Geriatrics Center and National Institute of Aging under award number P30 AG024824 (CAA, SVB), the Department of Defense and Congressionally Directed Medical Research Program W81XWH2010336 (CAA, YCJ) and W81XWH-18-1-0653 and W81XWH-20-1-0795 (BDL), PCF Young Investigator Award and a Department of Defense Idea Development Award (SP), and the National Science Foundation Graduate Research Fellowship Program under Grant Number DGE 1256260 (JL). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or National Science Foundation. Publisher Copyright: {\textcopyright} 2021, eLife Sciences Publications Ltd. All rights reserved.",
year = "2021",
month = jul,
doi = "10.7554/eLife.66749",
language = "English (US)",
volume = "10",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}