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      The Satellite Cell at 60: The Foundation Years

      review-article
      , *
      ,
      Journal of Neuromuscular Diseases
      IOS Press
      Satellite cell, skeletal muscle, muscle regulatory factors, muscle regeneration, myofibre, Pax7, MyoD, Myf5

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          Abstract

          The resident stem cell for skeletal muscle is the satellite cell. On the 50th anniversary of its discovery in 1961, we described the history of skeletal muscle research and the seminal findings made during the first 20 years in the life of the satellite cell (Scharner and Zammit 2011, doi: 10.1186/2044-5040-1-28). These studies established the satellite cell as the source of myoblasts for growth and regeneration of skeletal muscle. Now on the 60th anniversary, we highlight breakthroughs in the second phase of satellite cell research from 1980 to 2000. These include technical innovations such as isolation of primary satellite cells and viable muscle fibres complete with satellite cells in their niche, together with generation of many useful reagents including genetically modified organisms and antibodies still in use today. New methodologies were combined with description of endogenous satellite cells markers, notably Pax7. Discovery of the muscle regulatory factors Myf5, MyoD, myogenin, and MRF4 in the late 1980s revolutionized understanding of the control of both developmental and regerenative myogenesis. Emergence of genetic lineage markers facilitated identification of satellite cells in situ, and also empowered transplantation studies to examine satellite cell function. Finally, satellite cell heterogeneity and the supportive role of non-satellite cell types in muscle regeneration were described. These major advances in methodology and in understanding satellite cell biology provided further foundations for the dramatic escalation of work on muscle stem cells in the 21st century.

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          Most cited references218

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          Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

          Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to mouse embryonic development. These data demonstrate that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors.
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            Dystrophin: the protein product of the Duchenne muscular dystrophy locus.

            The protein product of the human Duchenne muscular dystrophy locus (DMD) and its mouse homolog (mDMD) have been identified by using polyclonal antibodies directed against fusion proteins containing two distinct regions of the mDMD cDNA. The DMD protein is shown to be approximately 400 kd and to represent approximately 0.002% of total striated muscle protein. This protein is also detected in smooth muscle (stomach). Muscle tissue isolated from both DMD-affected boys and mdx mice contained no detectable DMD protein, suggesting that these genetic disorders are homologous. Since mdx mice present no obvious clinical abnormalities, the identification of the mdx mouse as an animal model for DMD has important implications with regard to the etiology of the lethal DMD phenotype. We have named the protein dystrophin because of its identification via the isolation of the Duchenne muscular dystrophy locus.
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              Satellite cells are essential for skeletal muscle regeneration: the cell on the edge returns centre stage.

              Following their discovery in 1961, it was speculated that satellite cells were dormant myoblasts, held in reserve until required for skeletal muscle repair. Evidence for this accumulated over the years, until the link between satellite cells and the myoblasts that appear during muscle regeneration was finally established. Subsequently, it was demonstrated that, when grafted, satellite cells could also self-renew, conferring on them the coveted status of 'stem cell'. The emergence of other cell types with myogenic potential, however, questioned the precise role of satellite cells. Here, we review recent recombination-based studies that have furthered our understanding of satellite cell biology. The clear consensus is that skeletal muscle does not regenerate without satellite cells, confirming their pivotal and non-redundant role.
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                Author and article information

                Journal
                J Neuromuscul Dis
                J Neuromuscul Dis
                JND
                Journal of Neuromuscular Diseases
                IOS Press (Nieuwe Hemweg 6B, 1013 BG Amsterdam, The Netherlands )
                2214-3599
                2214-3602
                10 September 2021
                30 November 2021
                2021
                : 8
                : Suppl 2 , Special Issue Dedicated to Professor Terence Partridge
                : S183-S203
                Affiliations
                [1]Randall Centre for Cell and Molecular Biophysics , King’s College London, Guy’s Campus, London, SE1 1UL, UK
                Author notes
                [* ]Correspondence to: Randall Centre for Cell and Molecular Biophysics, King’s College London, Guy’s Campus, London, SE1 1UL, UK. E-mail: peter.zammit@ 123456kcl.ac.uk .
                [ 1 ]

                ORCID iD: 0000-0001-9562-3072

                Author information
                https://orcid.org/0000-0001-9562-3072
                Article
                JND210705
                10.3233/JND-210705
                8673500
                34459412
                887d9e2a-7bdc-401b-b9c7-41358218a59d
                © 2021 – The authors. Published by IOS Press

                This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Review

                satellite cell,skeletal muscle,muscle regulatory factors,muscle regeneration,myofibre,pax7,myod,myf5

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