The space industry has made significant strides, leading to an era of commercial spaceflight. Meanwhile, understanding molecular responses to spaceflight is crucial for astronauts' safety. To this end, we examined transcriptomic and epigenetic changes in two astronauts' blood samples at three timepoints: two weeks before spaceflight (T0), 24 hours after spaceflight (T2), and three months after spaceflight (T3). Transcriptomic analysis identified two gene clusters with opposing transient expression trends post-flight (T2), normalized at T3: one upregulated and the other downregulated. Mapped immune cell types through the CIBERSORT coupled with the pathway analysis suggested monocytes' role in coordinated cellular response. Epigenetic analysis identified four methylation patterns with transient and persistent changes post-flight, enriched in nervous system development and cell apoptosis pathways. Methylation changes implicated genes associated with bone disorders, including FBLIM1, IHH, and SCAMP2. eQTM analysis suggested a link between RNA transcriptional level and DNA methylation through transcriptional regulator ZNF684. In conclusion, our study revealed significant short-term transcriptional and methylation changes as well as long-term methylation changes. This study hosts the RNAseq dataset. DNA methylation dataset can be found in OSD-943.

The space industry has made significant strides, leading to an era of commercial spaceflight. Meanwhile, understanding molecular responses to spaceflight is crucial for astronauts' safety. To this end, we examined transcriptomic and epigenetic changes in two astronauts' blood samples at three timepoints: two weeks before spaceflight (T0), 24 hours after spaceflight (T2), and three months after spaceflight (T3). Transcriptomic analysis identified two gene clusters with opposing transient expression trends post-flight (T2), normalized at T3: one upregulated and the other downregulated. Mapped immune cell types through the CIBERSORT coupled with the pathway analysis suggested monocytes' role in coordinated cellular response. Epigenetic analysis identified four methylation patterns with transient and persistent changes post-flight, enriched in nervous system development and cell apoptosis pathways. Methylation changes implicated genes associated with bone disorders, including FBLIM1, IHH, and SCAMP2. eQTM analysis suggested a link between RNA transcriptional level and DNA methylation through transcriptional regulator ZNF684. In conclusion, our study revealed significant short-term transcriptional and methylation changes as well as long-term methylation changes. This study hosts the DNA methylation dataset. RNAseq dataset can be found in OSD-903.