An Epigenetic Trigger for Induction of Genomic Plasticity Following Exposure to Space Environment: Mission SpaceX CRS-19 RRR-1 [RNA-seq]

Genomic plasticity helps adapt to extreme environmental conditions. We tested the hypothesis that exposure to space environment (ESE) impacts the epigenome as marked by DNA hypomethylation to induce genomic plasticity in responders. Murine skin samples from the Rodent Research Reference Mission-1 were procured from the International Space Station (ISS) National Lab. Targeted RNA sequencing to test differential gene expression between the skin of ESE versus ground controls revealed upregulation of VEGF mediated angiogenesis pathways secondary to promoter hypomethylation in responder ESE cohort. Methylome sequencing identified ESE-sensitive candidate hypomethylated genes including developmental angiogenic genes Araf, VegfbandVegfr1. Based on differentially expressed genes, the angiogenesis biofunction was enriched in responders compared to non-responders. The induction of genomic plasticity in response to ESE, as reported herein, may be viewed as a mark of biological resilience that is evident in a minority of organisms, responders but not in non-responders, exposed to the same stressor. Inducible genomic plasticity may be implicated in natural resilience to ESE. Femoral skin samples from 35 young (~10-16 weeks) female BALB/cAnNTac mice (Taconic Biosciences) were obtained through the International Space Station (ISS) National Laboratory’s Biospecimen Sharing Program, and no live animals were involved in this study. These mice belonged to the SpaceX CRS-19 Rodent Research-8 mission [also known as Rodent Research Reference Mission-1 (RRR1)] were procured from ISS National Laboratory in collaboration with Dr. Liz Warren. The detailed information regarding the RRR-1 mission is available through ISS laboratory’s Center for the Advancement of Science in Space (CASIS) research archive (www.iss-casis.org/research-on-the-iss/solicitations/2018-rodent-research/). Briefly, this study investigated skin samples from 17 mice that were flown to space (10 euthanized in space; 8 euthanized post-landing) for a total of ~40 days and 18 mice age-matched ground control animals.For targeted RNA sequencing, total RNA was extracted using ABI Picopure RNA isolation kit and quality assessment was performed using Agilent 2100 Bioanalyzer.