Abstract
Muscle regeneration is an important homeostatic process of adult skeletal muscle that recapitulates many aspects of embryonic myogenesis. Satellite cells (SCs) are the main muscle stem cells responsible for skeletal muscle regeneration. SCs reside between the myofiber basal lamina and the sarcolemma of the muscle fiber in a quiescent state. However, in response to physiological stimuli or muscle trauma, activated SCs transiently re-enter the cell cycle to proliferate and subsequently exit the cell cycle to differentiate or self-renew. Recent evidence has stated that SCs display functional heterogeneity linked to regenerative capability with an undifferentiated subgroup that is more prone to self-renewal, as well as committed progenitor cells ready for myogenic differentiation. Several lineage tracing studies suggest that such SC heterogeneity could be associated with different embryonic origins. Although it has been established that SCs are derived from the central dermomyotome, how a small subpopulation of the SCs progeny maintain their stem cell identity while most progress through the myogenic program to construct myofibers is not well understood. In this review, we synthesize the works supporting the different developmental origins of SCs as the genesis of their functional heterogeneity.
Highlights
Muscle repair and homeostasis are mediated by resident stem cells, called Satellite cells (SCs)
Quiescent SCs are characterized by the expression of the transcription factor Pax7 but, upon acute injury, pathological conditions or muscle homeostasis, they become activated and give rise to myogenic progenitors that massively proliferate, start to express the myogenic regulatory factors (MRFs) Myf5, Myod1, Myf6, and Myog, differentiate and fuse to form new myofibers and restore the muscle tissue
Behavioral heterogeneity has been observed in myogenic precursors during development, given the differences in proliferative rate observed in dermomyotome-derived progenitors during embryonic myogenesis and MRF expression patterns in fetal and perinatal stages, despite their functional redundancy (Gros et al, 2005; Kassar-Duchossoy et al, 2005; Picard and Marcelle, 2013)
Summary
Muscle repair and homeostasis are mediated by resident stem cells, called SCs. Anatomically, SCs are located between the myofiber basal lamina and the sarcolemma of the muscle fiber and functionally are quiescent cells. Quiescent SCs are characterized by the expression of the transcription factor Pax but, upon acute injury, pathological conditions or muscle homeostasis, they become activated and give rise to myogenic progenitors that massively proliferate, start to express the myogenic regulatory factors (MRFs) Myf, Myod, Myf ( known as MRF4), and Myog, differentiate and fuse to form new myofibers and restore the muscle tissue. It is well known that SCs and developmental myogenic progenitors share the transcriptional program that drives myogenic differentiation and muscle. Behavioral heterogeneity has been observed in myogenic precursors during development, given the differences in proliferative rate observed in dermomyotome-derived progenitors during embryonic myogenesis and MRF expression patterns in fetal and perinatal stages, despite their functional redundancy (Gros et al, 2005; Kassar-Duchossoy et al, 2005; Picard and Marcelle, 2013). We summarize the latest research evidence on SC functional heterogeneity and examine the principles that sustain myogenic progenitor pool diversity of SCs of somitic origin and the implications for the emergence of SC heterogeneity
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