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The Skeletal Muscle Satellite Cell: The Stem Cell That Came in From the Cold

Peter S. Zammit, Terence A. Partridge and Zipora Yablonka-Reuveni

Randall Division of Cell and Molecular Biophysics, King's College London, London, England (PSZ); Children's National Medical Center, Washington, DC (TAP); and Department of Biological Structure and Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, University of Washington, Seattle, Washington (ZY-R)

Correspondence to: Dr. Peter Zammit, Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL England. E-mail: peter.zammit{at}kcl.ac.uk. Co-corresponding author: Dr. Zipora Yablonka-Reuveni. E-mail: reuveni{at}u.washington.edu

The muscle satellite cell was first described and actually named on the basis of its anatomic location under the basement membrane surrounding each myofiber. For many years following its discovery, electron microscopy provided the only definitive method of identification. More recently, several molecular markers have been described that can be used to detect satellite cells, making them more accessible for study at the light microscope level. Satellite cells supply myonuclei to growing myofibers before becoming mitotically quiescent in muscle as it matures. They are then activated from this quiescent state to fulfill their roles in routine maintenance, hypertrophy, and repair of adult muscle. Because muscle is able to efficiently regenerate after repeated bouts of damage, systems must be in place to maintain a viable satellite cell pool, and it was proposed over 30 years ago that self-renewal was the primary mechanism. Self-renewal entails either a stochastic event or an asymmetrical cell division, where one daughter cell is committed to differentiation whereas the second continues to proliferate or becomes quiescent. This classic model of satellite cell self-renewal and the importance of satellite cells in muscle maintenance and repair have been challenged during the past few years as bone marrow-derived cells and various intramuscular populations were shown to be able to contribute myonuclei and occupy the satellite cell niche. This is a fast-moving and dynamic field, however, and in this review we discuss the evidence that we think puts this enigmatic cell firmly back at the center of adult myogenesis. (J Histochem Cytochem 54:1177–1191, 2006)

Key Words: satellite cell • stem cell • myogenesis • myoblast • skeletal muscle • Pax7 • self-renewal • regeneration • MyoD • aging

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