The muscle satellite cell at 50: the formative years

Abstract

In February 1961, Alexander Mauro described a cell 'wedged' between the plasma membrane of the muscle fibre and the surrounding basement membrane. He postulated that it could be a dormant myoblast, poised to repair muscle when needed. In the same month, Bernard Katz also reported a cell in a similar location on muscle spindles, suggesting that it was associated with development and growth of intrafusal muscle fibres. Both Mauro and Katz used the term 'satellite cell' in relation to their discoveries. Today, the muscle satellite cell is widely accepted as the resident stem cell of skeletal muscle, supplying myoblasts for growth, homeostasis and repair.Since 2011 marks both the 50th anniversary of the discovery of the satellite cell, and the launch of Skeletal Muscle, it seems an opportune moment to summarise the seminal events in the history of research into muscle regeneration. We start with the 19th-century pioneers who showed that muscle had a regenerative capacity, through to the descriptions from the mid-20th century of the underlying cellular mechanisms. The journey of the satellite cell from electron microscope curio, to its gradual acceptance as a bona fide myoblast precursor, is then charted: work that provided the foundations for our understanding of the role of the satellite cell. Finally, the rapid progress in the age of molecular biology is briefly discussed, and some ongoing debates on satellite cell function highlighted.

Figure 1

Timeline of some seminal events in the history of muscle regeneration.

Figure 2

The first mammalian satellite cell. The electron micrograph of a mammalian satellite cell from Mauro's 1961 paper [6]. Described in his own words: 'Transverse section of a skeletal muscle fiber from the rat sartorius, furnished by courtesy of Dr. G. Palade. As in Fig. 9, the apposing plasma membranes of the satellite cell (sp) and the muscle cell (mp) are seen at the inner border of the satellite cell. The basement membrane (bm) can be seen extending over the "gap" between the plasma membrane of the muscle cell and the satellite cell. Methacrylate embedding. Stained with PbOH. × 22,000'. ^© The Rockefeller University Press. J Biophys Biochem Cytol 1961, 9:493-495.

Figure 3

Images of cultivated chick embryonic muscle from 1917. Two images of chick muscle in culture from Lewis and Lewis, 1917 [34]. The image on the left is outgrowth from leg muscle of a 7-day-old chick embryo cultivated in half Locke's solution, half bouillon plus 0.5% dextrose for 48 hours. The preparation was fixed in osmic acid vapour and a Benda stain used. Lewis and Lewis describe it thus: 'Somewhat different character of muscle outgrowth from an explanted piece of the same leg and cultivated in the same way as in figure 1. The enlarged protoplasmic ends are not so abundant. There are many isolated muscle fibers and myoblasts among the mesenchyme cells. × 100' (originally figure 2 of Lewis and Lewis, 1917 [34]). The image on the right is of a 'myotube' from an explanted piece of leg of an 8-day-old chick embryo, fixed in osmic acid vapour, and stained with iron haematoxylin at × 525 (originally figure 8 of Lewis and Lewis, 1917 [34]). ^© John Wiley & Sons, Inc. Am J Anat 1917, 2:169-194. This material is reproduced with permission of John Wiley & Sons, Inc.

Figure 4

A mouse satellite cell in its niche on an isolated myofibre. A myofibre isolated from the extensor digitorum longus muscle of an adult mouse. The associated quiescent satellite cell was coimmunostained for Pax7 and caveolin 1. Nuclei were counterstained with 4',6-diamidino-2-phenylindole (DAPI), revealing the location of the myonuclei in the myofibre. Scale bar = 20 μm.