Insights into muscle stem cell dynamics during postnatal development

Abstract

During development, resident stem cell populations contribute to the growth and maturation of tissue and organs. In skeletal muscle, muscle stem cells, or satellite cells (SCs), are responsible for the maturation of postnatal myofibers. However, the role SCs play in later stages of postnatal growth, and thus, when they enter a mature quiescent state is controversial. Here, we discuss the current literature regarding the role SCs play in all stages of postnatal growth, from birth to puberty onset to young adulthood. We additionally highlight the implications of SC loss or dysfunction during developmental stages, both in the context of experimental paradigms and disease settings.

Keywords: aging; cancer; cerebral palsy; development; neuromuscular; pediatric; regeneration; satellite cells; skeletal muscle.

Figure 1.

Illustration comparing the developmental life cycle of mice and humans. Information is adapted from Dutta and Sengupta, 2016 [23].

Figure 2.

Representation of murine myofiber growth during postnatal stages. The majority of myonuclear accretion occurs prior to P21 [29]. However, during prepuberty, residual addition of myonuclei occurs to support myofiber growth [30, 34, 35, 39, 45]. As development proceeds, the cycling SC pool is reduced in number until the adult quiescent pool size is established at P56 [30, 45].

Figure 3.

Illustration depicting the potential developmental signals governing the progression of SCs to quiescence. The induction of sex hormones has been shown to induce Mib1 expression in myofibers, leading to elevated Notch signaling in cycling SCs [48]. Additionally, whole muscle RNA Sequencing has suggested alterations in ECM composition around the time of puberty onset [30]. However, the effect of the development and maturation of the ECM on SC fate has yet to be examined.

Figure 4.

Schematic representation of studies that have depleted SCs/genetically disrupted myonuclear contribution during postnatal growth. The major findings of these individual experiments have been listed in the included table. Due to consistency of myonuclear counts being performed on a myonuclei per millimeter basis (MN/mm), the percent decrease has been listed for the respective muscle. However, assessment of CSA was performed both in crosssection and on fixed myofibers, so only general trends have been listed.