The MyoGravity project to study real microgravity effects on human muscle precursor cells and tissue

Area of Science:

• Space biology and physiology
• Skeletal muscle adaptation
• Cellular and molecular biology

Background:

• Spaceflight microgravity causes skeletal muscle atrophy.
• Satellite cells (muscle precursor cells) are crucial for muscle maintenance and regeneration.
• Limited data exist on microgravity's effects on human satellite cells and muscle post-flight.

Purpose of the Study:

• To analyze cellular and transcriptional changes in human muscle precursor cells (huMPCs) exposed to real microgravity.
• To investigate the response of human skeletal muscle to Earth's gravity after prolonged spaceflight.
• To assess the functional impact of microgravity on astronaut satellite cells and muscle tissue.

Main Methods:

• Cultured differentiating huMPCs from astronaut muscle biopsies under microgravity (ISS) and standard gravity (1g) conditions.
• Performed transcriptomic analysis (RNA-Seq) on huMPCs and skeletal muscle tissue (pre- and post-flight).
• Evaluated satellite cell responsiveness, proliferation, and fusion capacity.

Main Results:

• Microgravity-exposed huMPCs showed altered gene expression: upregulated cell adhesion, downregulated muscle contraction machinery and myomiRs.
• Prolonged microgravity exposure impaired astronaut satellite cell function, reducing responsiveness, proliferation, and fusion.
• Post-flight muscle tissue exhibited prompt activation of muscle structure genes but downregulation of myelination and neuromuscular junction genes.

Conclusions:

• Real microgravity significantly alters human muscle precursor cell biology and function.
• Astronaut skeletal muscles show rapid mechanical readaptation but delayed recovery of nerve-related pathways post-flight.
• Impaired satellite cell function suggests a potential for inefficient muscle regeneration in astronauts after long-duration missions.