Steep increase in myonuclear domain size during infancy

Area of Science:

• Muscle physiology
• Developmental biology
• Cell biology

Background:

• Skeletal muscle growth involves increases in muscle fiber size (hypertrophy).
• The relationship between myonuclear accretion and fiber growth during human development is not fully understood.
• Satellite cells are muscle stem cells crucial for muscle repair and growth.

Purpose of the Study:

• To investigate if myonuclear number increases proportionally with fiber size during skeletal muscle maturation in children.
• To examine the changes in satellite cell density and myonuclear number relative to fiber cross-sectional area (FCSA) with age.
• To determine the developmental trajectory of myonuclear domain size.

Main Methods:

• Human thoraco-abdominal muscle tissue samples were collected from 6-day to 15-year-old children.
• Muscle cross-sections were stained for laminin (basal lamina) and DAPI (nuclei).
• Fiber cross-sectional area (FCSA) was measured, and myonuclei (pax7-negative) and satellite cells (pax7-positive) were quantified.

Main Results:

• Fiber cross-sectional area (FCSA) increased significantly with age (187 μm²/year).
• Satellite cell density decreased sharply in early life, without a concurrent rise in myonuclei per fiber.
• Myonuclear number per fiber remained stable until age four, then increased, while myonuclear domain size expanded significantly during infancy and childhood.

Conclusions:

• Myonuclear addition does not keep pace with fiber growth in early childhood.
• Significant increases in myonuclear number occur after four years of age, supporting the concept of myonuclear domain regulation.
• Myonuclear domain size expands considerably during early development, reaching adult proportions in adolescence.