A Comprehensive DNA Methylome BodyMap across 12 Organs/Tissues from Spaceflight Mice

Area of Science:

• Space biology and epigenetics.
• Mammalian physiology under extreme environments.

Background:

• Spaceflight induces physiological stress, including microgravity and radiation, prompting molecular adaptations.
• The systemic and temporal effects of spaceflight on epigenetic regulation are not well understood.

Purpose of the Study:

• To create a comprehensive DNA methylome map across multiple organs in mice exposed to long-duration spaceflight.
• To investigate the tissue-specific and temporal dynamics of spaceflight-induced epigenetic changes.
• To integrate DNA methylation data with transcriptome data to understand molecular responses.

Main Methods:

• Reduced Representation Bisulfite Sequencing (RRBS) was used to profile the DNA methylome across 12 organs/tissues from spaceflight mice at three time points.
• RNA sequencing (RNA-seq) was performed on five organs and integrated with methylome data.
• Functional enrichment analysis was conducted on differentially methylated CpGs (DMCs).

Main Results:

• Spaceflight induced limited, but highly tissue-specific, differentially methylated CpGs (DMCs).
• Most methylation changes returned to baseline levels within one to six months after flight.
• Functional analysis revealed common metabolic and mitochondrial dysregulation, alongside tissue-specific developmental responses in immune, reproductive, and structural tissues.
• Transcriptome data indicated suppressed immune and increased inflammatory responses, mimicking aging.

Conclusions:

• This study provides a comprehensive DNA methylome BodyMap across 12 organs/tissues in spaceflight mice.
• It elucidates the tissue specificity of epigenetic alterations induced by spaceflight.
• These findings are vital for developing biomarkers and countermeasures to protect astronaut health during long-duration missions.