Prepubertal skeletal muscle growth requires Pax7-expressing satellite cell-derived myonuclear contribution

Area of Science:

• Muscle biology
• Developmental biology
• Cellular mechanisms

Background:

• The role of Pax7-expressing satellite cells (SCs) in postnatal skeletal muscle growth after weaning is not well understood.
• Prepubertal skeletal muscle development, a critical growth phase, has not been previously examined regarding SC function.

Purpose of the Study:

• To investigate the functional role of SCs in mouse skeletal muscle growth during the prepubertal period.
• To characterize gene expression changes and SC-derived myonuclear contribution during prepubertal development.

Main Methods:

• Characterization of mouse skeletal muscle growth during prepuberty.
• Genome-wide RNA-sequencing to analyze gene expression signatures.
• Indelible labeling of SCs using Pax7;Rosa26 mice to track myonuclear contribution.
• Depletion of SCs to assess their impact on muscle growth and function.

Main Results:

• Significant increases in myofiber cross-sectional area correlated with SC-derived myonuclear number during prepuberty.
• Distinct gene expression profiles were observed between juvenile and early adolescent skeletal muscle, indicating maturation.
• SCs contributed significantly to myonuclear number during prepuberty, with reduced contribution at puberty onset.
• Prepubertal SC depletion impaired myofiber size, myonuclear number, and force generation in both fast and slow muscles.

Conclusions:

• SC-derived myonuclear accretion is a key cellular mechanism for prepubertal hypertrophic skeletal muscle growth.
• The prepubertal period is characterized by significant skeletal muscle maturation involving SCs.
• SCs play a vital role in establishing muscle mass and function before puberty.