Safely Traveling through Space: The Final Frontier for Epigenetic and Transcriptomic Analyses?

By Stuart P. Atkinson

Blood transcriptomics changes in astronauts. From Ao et al. The study was to investigate the impacts of short-duration spaceflight, where blood samples were drawn at pre-flight (T0), at post-flight (T2), and at the three months post-flight (T3). Clear clusters of genes show "V" and "A" profiles of spaceflight-induced transcriptional changes that return to baseline after three months.

Can We Pass the Final Frontier Safely?

While a vast fortune and a little bravery may appear the only real barriers to space travel to some, we are still only beginning to appreciate the harms associated with traveling beyond this "final frontier". The long-term confinement, radiation, and microgravity associated with space travel (alongside other factors; Afshinnekoo et al. and Durante & Cucinotta) have been linked to a host of detrimental consequences in humans, including cognitive impairment, muscle/bone deterioration, immune dysfunction, and cardiovascular health problems (Afshinnekoo et al., Strollo et al., and Hou et al.). Can we decipher the molecular mechanisms linking the stresses of space travel and human health in the hope of developing therapeutic approaches that would ensure the safety of astronauts and guide future space-related activities?

Multiomics-based studies of samples isolated from astronauts represent one exciting means of elucidating cellular and molecular responses to space travel (da Silveira et al. and Garrett-Bakelman et al.). In a small step that may lead to a giant leap in our understanding in this area, researchers from the laboratory of Luda Diatchenko (McGill University) employed a multiomics approach to examine the transcriptomic and epigenetic alterations occurring in easily accessible blood samples from two astronauts weeks before, and one day and three months after space travel. The results of this exciting new study, published in Scientific Reports (Ao et al.).

Read on to find out whether the findings of this space-age new study will safely and speedily move us beyond the final frontier, and if Paired-Tag technology from Epigenome Technologies can accelerate this area of research to warp speed!

Blood methylation epigenetics changes in astronauts. From Ao, et al.

Transcriptomic and Epigenetic Analyses Highlight Transient and Persistent Alterations in Immune Cells

The authors of this space-age study assessed the transcriptomic and DNA methylation profiles of two astronauts from blood samples isolated before and after the first all-private astronaut mission to the International Space Station (Axiom Space's AX-1) to explore molecular pattern dynamics in response to the stresses of space travel. Initial analyses of how immune cell types varied in population size over time (from transcriptomic and epigenetic analyses) suggested a reduction of circulating monocytes during space travel that recovers to baseline after the event, potentially as a response to associated physical or metabolic challenges. Overall, these data suggested significant but transient shifts in the immune system caused by the unique stressors of space travel.

The transcriptomic comparison between the three time points revealed no significant differences in gene expression due to the small number of participants evaluated; however, the results suggested that many genes underwent transient alterations in their expression during space travel. Those genes downregulated during space travel had links to "protein modification by small protein conjugation or removal pathway" and "regulation of macromolecule metabolic processes", and those genes upregulated had links to "regulation of metabolic process pathway", "pathways for response to hormones", and "autophagy regulation".

Genome-wide DNA methylation assays aimed to identify any short-/long-lasting epigenetic alterations associated with space travel; comparing DNA methylation levels between each pair of time points to identify any significant alterations revealed 924 differentially methylated probes corresponding to 919 genes that functioned in 945 significant pathways. Critical pathways involved macromolecular metabolic processes and nervous system development, which suggested that space travel impacts multiple body systems, prompting epigenetic adaptations in the immune and nervous systems. A temporal analysis of DNA methylation alterations suggested that most affected genes underwent transient silencing during space travel but highlighted the general commonality of more persistent alterations. Pathway enrichment analysis to explore the implications of these biological patterns suggested that persistent DNA methylation alterations due to the sustained impact of space travel on the human body extended to the systemic level and impacted pathways such as nervous system development, protein metabolic processes, and apoptotic signaling pathways. Moving from these regional analyses to analysis of individual CpGs revealed that five areas suffered from significant alterations in DNA methylation levels during space travel: three differentially methylated genes (FBLIM1, IHH,SCAMP2AK8 Juhl IV et al.).

Exploring relationships between DNA methylation and transcriptomic alterations revealed one significant result:ZNF684ZNF684ZNF684 Blengio et al.).

Association between gene ZNF684 expression and CpG cg21011110 methylation across time. From Ao, et al.

Can Epigenome Technologies Accelerate Space-based Research to Warp Speed

Although based on only two astronauts' blood samples, these findings revealed that space travel induced short-term transcriptional and DNA methylation alterations and long-term DNA methylation alterations in immune cells. These findings may provide a platform to identify means of counteracting space travel-related adverse impacts; however, the study must move beyond certain limitations including the small sample size, the lack of data representing the time of space travel itself, and the relatively short duration of the space travel when compared to the generally long duration of space missions to provide robust explorable targets.

This exciting study integrated transcriptomic data with DNA methylation data to provide mechanistic insights into the effects of space travel on blood cells; however, the authors noted the absence of data resources beyond gene expression and DNA methylation as another limitation to their study. Could the application of Paired-Tag technology reveal additional critical layers of epigenetic information, such as histone modification profiles, and link them to changes in RNA transcription in the same single cell to reveal more regarding the adverse impacts of space travel? Paired-Tag technology can also facilitate the transition from bulk-cell to single-cell analyses, potentially providing even greater insight. Paired-Tag technology from Epigenome Technologies generates joint epigenetic and transcriptomic profiles at single-cell resolution and detects histone modifications and RNA transcripts in individual nuclei with comparable efficiency to single-nucleus RNA-seq/ChIP-seq assays while avoiding the need for cell sorting. The implementation of Paired-Tag technology may enable these researchers to accelerate their studies into the safety of space travel to warp speed in the near future.