TY - JOUR TI - Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging AU - Larouche, Jacqueline A AU - Mohiuddin, Mahir AU - Choi, Jeongmoon J AU - Ulintz, Peter J AU - Fraczek, Paula AU - Sabin, Kaitlyn AU - Pitchiaya, Sethuramasundaram AU - Kurpiers, Sarah J AU - Castor-Macias, Jesus AU - Liu, Wenxuan AU - Hastings, Robert Louis AU - Brown, Lemuel A AU - Markworth, James F AU - De Silva, Kanishka AU - Levi, Benjamin AU - Merajver, Sofia D AU - Valdez, Gregorio AU - Chakkalakal, Joe V AU - Jang, Young C AU - Brooks, Susan V AU - Aguilar, Carlos A A2 - Tajbakhsh, Shahragim A2 - Kaeberlein, Matt VL - 10 PY - 2021 DA - 2021/07/29 SP - e66749 C1 - eLife 2021;10:e66749 DO - 10.7554/eLife.66749 UR - https://doi.org/10.7554/eLife.66749 AB - 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. KW - single cell RNA-seq KW - aging KW - neuromuscular junction KW - synapse JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -