Integrative analysis of space environment responsive gene networks

Abstract

Environmental changes are important factors that can cause crucial health and survival consequences for all domains of life. As such, twin studies indicated that environmental stressors account for more cancer cases than the inherited genetic code for particular cancer types. Space conditions present drastically different environmental conditions, such as different radiation levels and gravitational force. Given the elevated interest in human exploration of space, it is important to uncover the space-affected biological processes at the systems level. Currently, the studies at the International Space Station (ISS) introduce a combination of environmental stressors including microgravity exposure and dietary changes. Separate studies are required to discover the individual impact of each environmental stressor on biological processes. ☐ First, we investigated the intergenerational transcriptomic response to liquid cultivation and the response differences in a wild-isolate and the laboratory strain of C. elegans. The results revealed that the wild-isolate and the laboratory strain show vastly different transcriptomic responses to the same diet. Approximately 8% - 34% of liquid cultivation-induced transcriptomic responses are transmitted to the subsequent generation. ☐ Second, we tested the intergenerational dynamics of five histone modifications (H3K4me3, H3K9me3, H4K20me1, H3K27me3, H3K36me1) under liquid cultivation to better understand some of the underlying epigenetic mechanisms. Our results depicted that while H3K4me3 and H3K27me3 mostly maintained their distribution, the others demonstrated highly dynamic distributions on the chromosomes. These results indicate an adaptive function for H3K9me3, H4K20me1, and H3K36me1 in response to liquid cultivations. ☐ Third, we evaluated the sole impact of simulated microgravity during and after exposure. Through the integration of our in-house data with the publicly available datasets from NASA’s GeneLab, we determined a “gravitome” which we defined as the microgravity responsive transcriptomic signatures which are conserved between the worms and humans. ☐ Finally, we identified the Weighted Gene Co-expression Networks (WGCNA) for space responsive gene networks by integrating our RNA-seq data with publicly available ones from Gene Expression Omnibus for dietary changes (vitamin C, glucose, and glucosamine supplement) in worms. We identified 50 co-expressed gene networks (modules) and their putative drivers. We believe our combinatory approach can be generally applicable to other environmental stressors to facilitate the exploration of disease-driving genetic responses and create potential therapeutic targets.