Spaceflight multi-omics reveals vulnerabilities of human germ cell development.

Area of Science:

• Reproductive biology
• Space medicine
• Stem cell science

Background:

• Interplanetary exploration requires understanding spaceflight's effects on human reproduction.
• Direct studies of germ cell biology in orbit face technical challenges.

Purpose of the Study:

• To investigate the impact of spaceflight on human germ cell development.
• To establish a framework for monitoring cellular adaptation in space.

Main Methods:

• Utilized an automated bioreactor for long-term differentiation of human embryonic stem cells into hiPGCs, hiOFs, and hiSSCs.
• Employed integrated real-time imaging, perfusion, and in situ preservation for time-resolved multi-omics analysis.
• Conducted missions on China's Tianzhou-1 and Tianzhou-6 spacecraft.

Main Results:

• Spaceflight reduced hiPGC specification efficiency by ~50% and hiSSC proliferation by 26%.
• Transcriptome-translatome coordination revealed cell-type-specific dysregulation in ECM organization, microtubule dynamics, and lipid metabolism.
• Genomic integrity was preserved, as shown by whole-exome sequencing and DNA methylome analysis.

Conclusions:

• Spaceflight significantly perturbs human germ cell development.
• The developed bioreactor system provides a scalable framework for studying cellular adaptation during space missions.
• Findings are critical for ensuring reproductive health during long-duration space exploration.