Global transcriptomic analysis suggests carbon dioxide as an environmental stressor in spaceflight: A systems biology GeneLab case study

Afshin Beheshti,Sylvain V Costes,Egle Cekanaviciute,David J Smith

doi:10.1038/s41598-018-22613-1

Abstract

Spaceflight introduces a combination of environmental stressors, including microgravity, ionizing radiation, changes in diet and altered atmospheric gas composition. In order to understand the impact of each environmental component on astronauts it is important to investigate potential influences in isolation. Rodent spaceflight experiments involve both standard vivarium cages and animal enclosure modules (AEMs), which are cages used to house rodents in spaceflight. Ground control AEMs are engineered to match the spaceflight environment. There are limited studies examining the biological response invariably due to the configuration of AEM and vivarium housing. To investigate the innate global transcriptomic patterns of rodents housed in spaceflight-matched AEM compared to standard vivarium cages we utilized publicly available data from the NASA GeneLab repository. Using a systems biology approach, we observed that AEM housing was associated with significant transcriptomic differences, including reduced metabolism, altered immune responses, and activation of possible tumorigenic pathways. Although we did not perform any functional studies, our findings revealed a mild hypoxic phenotype in AEM, possibly due to atmospheric carbon dioxide that was increased to match conditions in spaceflight. Our investigation illustrates the process of generating new hypotheses and informing future experimental research by repurposing multiple space-flown datasets.

Highlights

Comprehensive analysis of molecular signatures, such as transcriptional profiling, has become a standard technique in space biosciences and typically generates more extensive data than is required for the specific topic of investigation
animal enclosure modules (AEMs) and vivarium housing (Fig. 1B) as ground controls, and compared global transcriptomic changes associated with different housing conditions
Principal component analysis (PCA) demonstrated obvious differences between individual AEM and vivarium samples for all conditions (Fig. 2A–C) except for mammary glands from rats (Fig. 2D). It is apparent from the percent variance in PC1 that clear separation occurs between the vivarium and AEM samples

Summary

Introduction

Comprehensive analysis of molecular signatures, such as transcriptional profiling, has become a standard technique in space biosciences and typically generates more extensive data than is required for the specific topic of investigation. Investigating spaceflight-induced changes in the transcriptome involves sending model organisms to orbit, such as rodents on the space shuttle (Space Transportation System program, STS), on satellites such as Bion-M1 (BF), or on the International Space Station (ISS) In these experiments multiple aspects of the environment are collectively altered. AEM has been used as the standard rodent enclosure without major modifications in spaceflight experiments from STS2 to Bion-M1 (BF)[3], and its more modern version called the Habitat module of the Rodent Research Hardware System is currently used on the ISS Both AEM and vivarium housing follow the standard guidelines for laboratory animal care, which require at least 15 square inches per >25 g adult rodent (NASA Johnson Space Center Animal Care and Use Handbook). By using a previously-established systems biology approach to combine multiple analysis methods[8] we are able to uncover a statistical consensus on molecular pathways being modified by the change in animal housing

Methods

Results

Conclusion