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.

Satellite cells are essential for skeletal muscle regeneration: the cell on the edge returns centre stage

“…Skeletal muscle regeneration was first properly described in the 1860s, but almost a century elapsed before the cellular mechanisms of this process were resolved (Scharner and Zammit, 2011). A series of pioneering papers published between 1960 and 1961 provided compelling evidence that multinucleated myofibres in both developing and regenerating muscle arise from the fusion of multiple myoblasts (Bintliff and Walker, 1960;Capers, 1960;Konigsberg et al, 1960;Pietsch, 1961;Stockdale and Holtzer, 1961).…”

“…A series of pioneering papers published between 1960 and 1961 provided compelling evidence that multinucleated myofibres in both developing and regenerating muscle arise from the fusion of multiple myoblasts (Bintliff and Walker, 1960;Capers, 1960;Konigsberg et al, 1960;Pietsch, 1961;Stockdale and Holtzer, 1961). Controversy surrounded the source of these myoblasts in regenerating muscle, with theories that they emanated from amitotic division of surviving myonuclei, from de-differentiation of viable myonuclei back into myoblasts, or from cells in the interstitium and/or circulation (reviewed by Scharner and Zammit, 2011). Concurrent with the confirmation of cell fusion as the mechanism of myotube formation, the satellite cell was discovered and proposed as a new candidate for providing such myoblasts (Katz, 1961;Mauro, 1961).…”

The Skeletal Muscle Satellite Cell

“…The capacity of skeletal muscle to regenerate was documented in the 19th century, but it took another century before researchers unveiled the cellular basis of myofiber formation and regeneration (reviewed in Scharner and Zammit 2011). Seminal studies that set the stage for current cell biology of muscle regeneration were published in early 1960s.…”

The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells

“…Quiescent satellite cells express the paired-box transcription factor Pax7 (Pax7 + /MyoD 2 ). When satellite cells become activated and re-enter the cell cycle, MyoD is expressed (Pax7 + /MyoD + ) in culture ex vivo or in response to injury and hypertrophic stimuli in vivo (Scharner and Zammit, 2011;Relaix and Zammit, 2012). MyoD binds to thousands of genes and induces chromatin modifications which presumably open up the chromatin for sequence-specific transcription factors (Cao et al, 2010).…”