Muscle Satellite Cell Structure, Proliferation and Fusion

Abstract

Skeletal muscle comprises some 30–40% of body mass, consisting mainly of contractile muscle fibres. For most vertebrates, survival is compromised by any serious loss of mobility arising from failure of efficient muscle function. This places a high priority on rapid and efficient repair and on a finely tuned adjustment in size and strength both during postnatal growth and on change in imposed workload. The muscle fibres themselves are syncytia containing large numbers of myonuclei, which are postmitotic and do not proliferate during growth or repair. Thus the functions of cellular replacement in this tissue fall largely, if not entirely on a small population of ‘satellite cells’, so‐called because of their position between the plasmalemma of the muscle fibre and the overlying basement membrane. The precise role of these cells and their relationships to other cell types are topics of current research and debate.

Key Concepts:

  • The differentiated skeletal muscle cell is an ‘end cell’ that cannot proliferate to replace itself.

  • The muscle satellite cell is the predominant identified source of myogenic cells for growth repair and regeneration of postnatal skeletal muscle.

  • The anatomically defined muscle satellite cell appears to be heterogeneous.

  • Non‐satellite cell sources of myogenic cells have been identified in skeletal muscle.

  • There is evidence of conversion of non‐satellite cells to a myogenic fate and of satellite cells to non‐myogenic fates but the importance of these processes in vivo has not been ascertained.

Keywords: stem cell; satellite cell; myogenesis; muscle regeneration; muscle growth; myopathy

Figure 1.

Simplified diagram of the skeletal muscle fibre and satellite cell. The fibre itself is a syncytium in which all of the nuclei (myonuclei) are postmitotic and dedicated to the synthesis of proteins of the myofibrillar contractile apparatus, the metabolic chains and the various control systems. Lying on the outside surface of the muscle fibre but enclosed by its basement membrane, is the satellite cell. This is the best authenticated source of myogenic cells for the growth, repair and regeneration of adult skeletal muscle.

Figure 2.

(a) Electron micrograph of a transverse section of skeletal muscle fibre and satellite cell. The satellite cell lies beneath the basement membrane (BM) of the muscle fibre but is distinct from the fibre itself, being separated by the plasmalemma of the fibre, 1, and its own plasmalemma, 2. (By courtesy of Dr. Simon Watkins, University of Pittsburgh.) (b) Photomicrograph of a single muscle fibre carrying a satellite cell from a mouse in which the Pax3 gene has been targeted to express green fluorescent protein (GFP). The nucleus of the green cell has also been immunostained for the protein Pax7 (Red), confirming that it is a satellite cell. The myonuclei of the underlying muscle fibre are stained blue with 4′,6‐diamidino‐2‐phenylindole (DAPI), a dye that intercalates between the bases of DNA dimer.

Figure 3.

The difference in pattern of satellite cell behaviour during growth and regeneration in the mouse. (a) During the first 3–4 weeks of postnatal life, mouse muscle fibres grow predominantly by addition of new myonuclei. This is achieved by rapid proliferation of a small number of satellite cells. The relationship between the number of satellite cells and the rate of addition of myonuclei to the fibre is such that most, if not all, cell divisions must be asymmetric: one cell from each division persisting as a proliferating cell, the second fusing immediately with the underlying fibre. This phase of growth appears to be dependent on expression of the Pax7 gene. (b) Beyond postnatal week 4 in the mouse, satellite cells become quiescent, addition of myonuclei to myofibres ceases and further growth is achieved by expansion of the domain of sarocplasm around each myonucleus. Subsequent activation of satellite cells, for example, in response to muscle fibre damage, evokes a quite different pattern of proliferation. Since satellite cells comprise some 2–5% of total fibre‐associated nuclei, in order to replace the resident muscle they must expand in number by at least 20–50‐fold over the 2–3 days of proliferation which characterises an acute regenerative response. To achieve this, requires a geometric expansion within a transit‐amplifying population; that is, a high proportion of symmetrical divisions to give serial doublings of cells that will mostly differentiate and fuse together to replace the missing muscle fibres.

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Partridge, Terence A(Jul 2012) Muscle Satellite Cell Structure, Proliferation and Fusion. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022530]