Muscle satellite cells adopt divergent fates: a mechanism for self-renewal?
Growth, repair, and regeneration of adult skeletal muscle depends on the persistence of satellite cells: muscle stem cells resident beneath the basal lamina that surrounds each myofiber. However, how the satellite cell compartment is maintained is unclear. Here, we use cultured myofibers to model muscle regeneration and show that satellite cells adopt divergent fates. Quiescent satellite cells are synchronously activated to coexpress the transcription factors Pax7 and MyoD. Most then proliferate, down-regulate Pax7, and differentiate. In contrast, other proliferating cells maintain Pax7 but lose MyoD and withdraw from immediate differentiation. These cells are typically located in clusters, together with Pax7-ve progeny destined for differentiation. Some of the Pax7+ve/MyoD-ve cells then leave the cell cycle, thus regaining the quiescent satellite cell phenotype. Significantly, noncycling cells contained within a cluster can be stimulated to proliferate again. These observations suggest that satellite cells either differentiate or switch from terminal myogenesis to maintain the satellite cell pool.
Muscle Cell Biology Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital Campus, Du Cane Rd., London W12 0NN, UK. peter.zammit@csc.mrc.ac.uk
Peter S
PS
Zammit
Jon P
JP
Golding
Yosuke
Y
Nagata
Valérie
V
Hudon
Terence A
TA
Partridge
Jonathan R
JR
Beauchamp
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D015536:Down-Regulation; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D017570:MyoD Protein / Q000378:metabolism; D051763:PAX7 Transcription Factor; D032496:Satellite Cells, Skeletal Muscle / Q000502:physiology*
D018398:Homeodomain Proteins; D017570:MyoD Protein; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse