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      Fusion and beyond: Satellite cell contributions to loading‐induced skeletal muscle adaptation

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          Abstract

          Satellite cells support adult skeletal muscle fiber adaptations to loading in numerous ways. The fusion of satellite cells, driven by cell‐autonomous and/or extrinsic factors, contributes new myonuclei to muscle fibers, associates with load‐induced hypertrophy, and may support focal membrane damage repair and long‐term myonuclear transcriptional output. Recent studies have also revealed that satellite cells communicate within their niche to mediate muscle remodeling in response to resistance exercise, regulating the activity of numerous cell types through various mechanisms such as secretory signaling and cell–cell contact. Muscular adaptation to resistance and endurance activity can be initiated and sustained for a period of time in the absence of satellite cells, but satellite cell participation is ultimately required to achieve full adaptive potential, be it growth, function, or proprioceptive coordination. While significant progress has been made in understanding the roles of satellite cells in adult muscle over the last few decades, many conclusions have been extrapolated from regeneration studies. This review highlights our current understanding of satellite cell behavior and contributions to adaptation outside of regeneration in adult muscle, as well as the roles of satellite cells beyond fusion and myonuclear accretion, which are gaining broader recognition.

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          Most cited references245

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          Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis.

          Efficient tissue regeneration is dependent on the coordinated responses of multiple cell types. Here, we describe a new subpopulation of fibro/adipogenic progenitors (FAPs) resident in muscle tissue but arising from a distinct developmental lineage. Transplantation of purified FAPs results in the generation of ectopic white fat when delivered subcutaneously or intramuscularly in a model of fatty infiltration, but not in healthy muscle, suggesting that the environment controls their engraftment. These cells are quiescent in intact muscle but proliferate efficiently in response to damage. FAPs do not generate myofibres, but enhance the rate of differentiation of primary myogenic progenitors in co-cultivation experiments. In summary, FAPs expand upon damage to provide a transient source of pro-differentiation signals for proliferating myogenic progenitors.
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            • Article: not found

            SATELLITE CELL OF SKELETAL MUSCLE FIBERS

              • Record: found
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              A Pax3/Pax7-dependent population of skeletal muscle progenitor cells.

              During vertebrate development, successive phases of embryonic and fetal myogenesis lead to the formation and growth of skeletal muscles. Although the origin and molecular regulation of the earliest embryonic muscle cells is well understood, less is known about later stages of myogenesis. We have identified a new cell population that expresses the transcription factors Pax3 and Pax7 (paired box proteins 3 and 7) but no skeletal-muscle-specific markers. These cells are maintained as a proliferating population in embryonic and fetal muscles of the trunk and limbs throughout development. Using a stable green fluorescent protein (GFP) reporter targeted to Pax3, we demonstrate that they constitute resident muscle progenitor cells that subsequently become myogenic and form skeletal muscle. Late in fetal development, these cells adopt a satellite cell position characteristic of progenitor cells in postnatal muscle. In the absence of both Pax3 and Pax7, further muscle development is arrested and only the early embryonic muscle of the myotome forms. Cells failing to express Pax3 or Pax7 die or assume a non-myogenic fate. We conclude that this resident Pax3/Pax7-dependent progenitor cell population constitutes a source of myogenic cells of prime importance for skeletal muscle formation, a finding also of potential value in the context of cell therapy for muscle disease.

                Author and article information

                Contributors
                kmurach@uark.edu
                kmurach@uark.edu , cpete4@uky.edu
                Journal
                FASEB J
                FASEB J
                10.1096/(ISSN)1530-6860
                FSB2
                The FASEB Journal
                John Wiley and Sons Inc. (Hoboken )
                0892-6638
                1530-6860
                04 September 2021
                October 2021
                : 35
                : 10 ( doiID: 10.1096/fsb2.v35.10 )
                : e21893
                Affiliations
                [ 1 ] The Center for Muscle Biology University of Kentucky Lexington Kentucky USA
                [ 2 ] Molecular Muscle Mass Regulation Laboratory, Exercise Science Research Center, Department of Health, Human Performance, and Recreation University of Arkansas Fayetteville Arkansas USA
                [ 3 ] Cell and Molecular Biology Program University of Arkansas Fayetteville Arkansas USA
                [ 4 ] Department of Athletic Training and Clinical Nutrition College of Health Sciences University of Kentucky Lexington Kentucky USA
                [ 5 ] Department of Physical Therapy College of Health Sciences University of Kentucky Lexington Kentucky USA
                [ 6 ] Department of Physiology College of Medicine University of Kentucky Lexington Kentucky USA
                Author notes
                [*] [* ] Correspondence

                Kevin A. Murach, Molecular Muscle Mass Regulation Laboratory, Exercise Science Research Center, Department of Health, Human Performance, and Recreation, 303 HPER Building, Exercise Science Research Center, 155 Stadium Drive, University of Arkansas, Fayetteville, AR 72701, USA.

                Email: kmurach@ 123456uark.edu

                Charlotte A. Peterson, Department of Physical Therapy and The Center for Muscle Biology, 900 S. Limestone, CTW 439, University of Kentucky, Lexington, KY 40536, USA.

                Email: cpete4@ 123456uky.edu

                Author information
                https://orcid.org/0000-0003-2783-7137
                Article
                FSB221893
                10.1096/fj.202101096R
                9293230
                34480776
                47aac3ae-4ed7-4c32-a41b-eccc00c1f4e7
                © 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 13 August 2021
                : 03 July 2021
                : 17 August 2021
                Page count
                Figures: 1, Tables: 0, Pages: 15, Words: 44828
                Funding
                Funded by: NIH , doi 10.13039/100000002;
                Funded by: National Institutes of Arthritis and Musculoskeletal and Skin Diseases
                Award ID: AR060701
                Award ID: AR071753
                Funded by: National Institute on Aging , doi 10.13039/100000049;
                Award ID: AG049086
                Award ID: AG063994
                Categories
                Reviews
                Reviews
                Custom metadata
                2.0
                October 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.7 mode:remove_FC converted:18.07.2022

                Molecular biology
                endurance exercise,extracellular vesicles,hypertrophy,muscle stem cells,myonuclei,regeneration,resistance exercise

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