Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/66749 |
| _version_ | 1818024977385914368 |
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| author | Jacqueline A Larouche Mahir Mohiuddin Jeongmoon J Choi Peter J Ulintz Paula Fraczek Kaitlyn Sabin Sethuramasundaram Pitchiaya Sarah J Kurpiers Jesus Castor-Macias Wenxuan Liu Robert Louis Hastings Lemuel A Brown James F Markworth Kanishka De Silva Benjamin Levi Sofia D Merajver Gregorio Valdez Joe V Chakkalakal Young C Jang Susan V Brooks Carlos A Aguilar |
| author_facet | Jacqueline A Larouche Mahir Mohiuddin Jeongmoon J Choi Peter J Ulintz Paula Fraczek Kaitlyn Sabin Sethuramasundaram Pitchiaya Sarah J Kurpiers Jesus Castor-Macias Wenxuan Liu Robert Louis Hastings Lemuel A Brown James F Markworth Kanishka De Silva Benjamin Levi Sofia D Merajver Gregorio Valdez Joe V Chakkalakal Young C Jang Susan V Brooks Carlos A Aguilar |
| author_sort | Jacqueline A Larouche |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T04:08:47Z |
| format | Article |
| id | doaj.art-1102e70e73174fe0b033c99e67010a4a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:08:47Z |
| publishDate | 2021-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-1102e70e73174fe0b033c99e67010a4a2022-12-22T02:02:46ZengeLife Sciences Publications LtdeLife2050-084X2021-07-011010.7554/eLife.66749Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with agingJacqueline A Larouche0https://orcid.org/0000-0001-9380-3547Mahir Mohiuddin1Jeongmoon J Choi2Peter J Ulintz3https://orcid.org/0000-0002-2037-8655Paula Fraczek4Kaitlyn Sabin5Sethuramasundaram Pitchiaya6Sarah J Kurpiers7Jesus Castor-Macias8Wenxuan Liu9Robert Louis Hastings10Lemuel A Brown11James F Markworth12Kanishka De Silva13Benjamin Levi14Sofia D Merajver15Gregorio Valdez16https://orcid.org/0000-0002-0375-4532Joe V Chakkalakal17https://orcid.org/0000-0002-8440-7312Young C Jang18https://orcid.org/0000-0002-9489-2104Susan V Brooks19Carlos A Aguilar20https://orcid.org/0000-0003-3830-0634Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States; Biointerfaces Institute, University of Michigan, Ann Arbor, United StatesParker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, United States; School of Biological Sciences, Georgia Institute of Technology, Atlanta, United States; Wallace Coulter Departmentof Biomedical Engineering, Georgia Institute of Technology, Atlanta, United StatesParker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, United States; School of Biological Sciences, Georgia Institute of Technology, Atlanta, United States; Wallace Coulter Departmentof Biomedical Engineering, Georgia Institute of Technology, Atlanta, United StatesDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, United States; Biointerfaces Institute, University of Michigan, Ann Arbor, United States; Internal Medicine-Hematology/Oncology, University of Michigan, Ann Arbor, United StatesDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, United States; Biointerfaces Institute, University of Michigan, Ann Arbor, United StatesDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, United States; Biointerfaces Institute, University of Michigan, Ann Arbor, United StatesMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, United StatesDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, United States; Biointerfaces Institute, University of Michigan, Ann Arbor, United StatesDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, United States; Biointerfaces Institute, University of Michigan, Ann Arbor, United StatesDepartment of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, United States; Department of Biomedical Engineering, University of Rochester Medical Center, Rochester, United States; Wilmot Cancer Institute, Stem Cell and Regenerative Medicine Institute, and The Rochester Aging Research Center, University of Rochester Medical Center, Rochester, United StatesDepartmentof Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, United States; Center for Translational Neuroscience, Robert J. and Nancy D. Carney Institute for Brain Science and Brown Institute for Translational Science, Brown University, Providence, United StatesDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United StatesDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United StatesDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, United States; Biointerfaces Institute, University of Michigan, Ann Arbor, United StatesDepartment of Surgery, University of Texas Southwestern, Dallas, United States; Childrens Research Institute and Center for Mineral Metabolism, Dallas, United States; Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, United StatesDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, United States; Internal Medicine-Hematology/Oncology, University of Michigan, Ann Arbor, United StatesDepartmentof Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, United States; Center for Translational Neuroscience, Robert J. and Nancy D. Carney Institute for Brain Science and Brown Institute for Translational Science, Brown University, Providence, United StatesDepartment of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, United States; Department of Biomedical Engineering, University of Rochester Medical Center, Rochester, United States; Wilmot Cancer Institute, Stem Cell and Regenerative Medicine Institute, and The Rochester Aging Research Center, University of Rochester Medical Center, Rochester, United StatesParker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, United States; School of Biological Sciences, Georgia Institute of Technology, Atlanta, United States; Wallace Coulter Departmentof Biomedical Engineering, Georgia Institute of Technology, Atlanta, United StatesDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, United States; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United StatesDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, United States; Biointerfaces Institute, University of Michigan, Ann Arbor, United States; Childrens Research Institute and Center for Mineral Metabolism, Dallas, United States; Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, United StatesDuring 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.https://elifesciences.org/articles/66749single cell RNA-seqagingneuromuscular junctionsynapse |
| spellingShingle | Jacqueline A Larouche Mahir Mohiuddin Jeongmoon J Choi Peter J Ulintz Paula Fraczek Kaitlyn Sabin Sethuramasundaram Pitchiaya Sarah J Kurpiers Jesus Castor-Macias Wenxuan Liu Robert Louis Hastings Lemuel A Brown James F Markworth Kanishka De Silva Benjamin Levi Sofia D Merajver Gregorio Valdez Joe V Chakkalakal Young C Jang Susan V Brooks Carlos A Aguilar Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging eLife single cell RNA-seq aging neuromuscular junction synapse |
| title | Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging |
| title_full | Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging |
| title_fullStr | Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging |
| title_full_unstemmed | Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging |
| title_short | Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging |
| title_sort | murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging |
| topic | single cell RNA-seq aging neuromuscular junction synapse |
| url | https://elifesciences.org/articles/66749 |
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