Characterization of Epigenetic Regulation in an Extraterrestrial Environment: The Arabidopsis Spaceflight Methylome [RNA-seq]
Ontology highlight
ABSTRACT: When germinated and grown on-board the ISS (International Space Station), plant do not exhibit abnormal structures but they do have altered growth habits and this project aims to investigate the molecular mechanisms that provide the foundation for the altered growth habits observed in orbit. APEX03-2 (Advanced Plant Experiment 03-2), also known as TAGES-ISA (Transgenic Arabidopsis Gene Expression System-Intracellular Signaling Architecture) specifically addresses the growth and molecular changes that occur in Arabidopsis thaliana plants during spaceflight by using molecular and genetic tools, and by asking fundamental questions regarding root structure, growth and cell wall remodeling may be answered. This investigation advances the fundamental understanding of the molecular biological responses to extraterrestrial environments. This understanding helps to further define the impacts of spaceflight on biological systems to better enable NASA’s future space exploration goals. https://www.nasa.gov/mission_pages/station/research/experiments/1059.html
Project description:When germinated and grown on-board the ISS (International Space Station), plant do not exhibit abnormal structures but they do have altered growth habits and this project aims to investigate the molecular mechanisms that provide the foundation for the altered growth habits observed in orbit. APEX03-2 (Advanced Plant Experiment 03-2), also known as TAGES-ISA (Transgenic Arabidopsis Gene Expression System-Intracellular Signaling Architecture) specifically addresses the growth and molecular changes that occur in Arabidopsis thaliana plants during spaceflight by using molecular and genetic tools, and by asking fundamental questions regarding root structure, growth and cell wall remodeling may be answered. This investigation advances the fundamental understanding of the molecular biological responses to extraterrestrial environments. This understanding helps to further define the impacts of spaceflight on biological systems to better enable NASA’s future space exploration goals. https://www.nasa.gov/mission_pages/station/research/experiments/1059.html
Project description:Bacillus pumilus SAFR-032 was originally isolated from the Jet Propulsion Lab Spacecraft Assembly Facility and thoroughly characterized for its enhanced resistance to UV irradiation and oxidative stress. This unusual resistance of SAFR-032 is of particular concern in the context of planetary protection and calls for development of novel disinfection techniques to prevent extraterrestrial contamination. Previously, spores of SAFR-032 were exposed for 18 months to a variety of space conditions on board the International Space Station to investigate its resistance to Mars conditions and space travel. Here, proteomic characterization of vegetative SAFR-032 cells from space-surviving spores is presented in comparison to a ground control. Vegetative cells of the first passage were processed and subjected to quantitative proteomics using tandem mass tags. Approximately 60% of all proteins encoded by SAFR-032 were identified and 301 proteins were differentially expressed among the strains. The functional analysis of differentially expressed proteins revealed the downregulation of proteins related to carbohydrate transport/metabolism and energy production/conversion, which was validated by enzymatic assays. The same space-surviving strains showed upregulation of proteins related to competitive growth and stress response. Observed protein profiles provide insights into the possible molecular mechanisms of B. pumilus SAFR-032 to adapt and resist extreme extraterrestrial environments.
Project description:Experimentation on the International Space Station has reached the stage where repeated and nuanced transcriptome studies are beginning to illuminate the structural and metabolic differences between plants grown in space compared to plants on the Earth. Genes that are important in setting up the spaceflight responses are being identified; their role in spaceflight physiological adaptation are increasingly understood, and the fact that different genotypes adapt differently is recognized. However, the basic question of whether these spaceflight responses are required for survival has yet to be posed, and the fundamental notion that spaceflight responses may be non-adaptive has yet to be explored. Therefore the experiments presented here were designed to ask if portions of the plant spaceflight response can be genetically removed without causing loss of spaceflight survival and without causing increased stress responses. The CARA experiment compared the spaceflight transcriptome responses of two Arabidopsis ecotypes, Col-0 and WS, as well as that of a PhyD mutant of Col-0. When grown with the ambient light of the ISS, phyD displayed a significantly reduced spaceflight transcriptome response compared to Col-0, suggesting that altering the activity of a single gene can actually improve spaceflight adaptation by reducing the transcriptome cost of physiological adaptation. The WS genotype showed and even simpler spaceflight transcriptome response in the ambient light of the ISS, more broadly indicating that the plant genotype can be manipulated to reduce the transcriptome cost of plant physiological adaptation to spaceflight and suggesting that genetic manipulation might further reduce, or perhaps eliminate the metabolic cost of spaceflight adaptation. When plants were germinated and then left in the dark on the ISS, the WS genotype actually mounted a larger transcriptome response than Col-0, suggesting that the in-space light environment affects physiological adaptation, which further implies that manipulating the local habitat can also substantially impact the metabolic cost of spaceflight adaptation.
Project description:Spaceflight triggers molecular signal of apoptosis and inhibits cell migration to impede bone fracture repair in male mice Activated apoptosis and inhibited cell migration. Adverse impacts of spaceflight on musculoskeletal health increases the risk of bone fracture and impaired healing. Its yet elusive molecular comprehension warrants an immediate attention in the advent of increasingly frequent space travels. Here we examined the effect of spaceflight on bone healing using a 2mm femoral segmental bone defect (SBD) model. Forty, 9-week old, C57BL/6J male mice were randomized by cage into spaceflight or ground groups; 10 mice from spaceflight or ground groups, respectively underwent SBD surgery and rest served as unoperated sham controls. Surgery/sham procedures occurred 4 days prior to launch, thereafter the spaceflight mice were housed in the rodent habitat at International Space Station for around 4 weeks before their euthanasia. Feeding on same diet, the ground sham/surgery mice were in equivalent housing condition. The right leg femur from half of the spaceflight and ground groups were investigated by micro-computed tomography (µCT). In parallel, the callus regions from surgery groups and corresponding femoral segments in sham mice were probed by global transcriptomics and metabolomics assay. µCT confirmed escalated bone loss in sham spaceflight; and a concomitant trend towards habituation was highlighted by gene-metabolite networks linked to active cellular homeostasis and inhibited morbidity signal in sham spaceflight. The morbidity signal was switched in the spaceflight surgery mice and µCT analyses of spaceflight callus revealed an increased trabeculae spacing and decreased trabecular connectivity. Activated apoptotic signal in spaceflight callus was synchronized with inhibited cell migration signal that was critical for wounds to recruit growth factors, cytokines, and angiogenic agents. A major pro-apoptotic and anti-migration signal, namely RANK-NFκB axis emerged as the central node in spaceflight callus. Concluding, SBD in spaceflight triggered a unique biomolecular mechanism to meet failed regeneration, which merits a customized intervention strategy.
Project description:Spaceflight induces hepatic damage, partially owing to oxidative stress caused by the space environment such as microgravity and space radiation. We examined the roles of anti-oxidative sulfur-containing compounds on hepatic damage after spaceflight. We analyzed the livers of mice on board the International Space Station for 30 days. During spaceflight, half of the mice were exposed to artificial earth gravity (1 g) using centrifugation cages. Sulfur-metabolomics of the livers of mice after spaceflight revealed a decrease in sulfur antioxidants (ergothioneine, glutathione, cysteine, taurine, thiamine, etc.) and their intermediates (cysteine sulfonic acid, hercynine, N-acethylserine, serine, etc.) compared to the controls on the ground. Furthermore, RNA-sequencing showed upregulation of gene sets related to oxidative stress and sulfur metabolism, and downregulation of gene sets related to glutathione reducibility in the livers of mice after spaceflight, compared to controls on the ground. These changes were partially mitigated by exposure to 1 g centrifugation. For the first time, we observed a decrease in sulfur antioxidants based on a comprehensive analysis of the livers of mice after spaceflight. Our data suggest that a decrease in sulfur-containing compounds owing to both microgravity and other spaceflight environments (radiation and stressors) contributes to liver damage after spaceflight.
Project description:While it has been shown that astronauts suffer immune disorders after spaceflight, the underlying causes are still poorly understood and there are many variables to consider when investigating the immune system in a complex environment. Additionally, there is growing evidence that suggests that not only is the immune system being altered, but the pathogens that infect the host are significantly influenced by spaceflight and ground-based spaceflight conditions. In this study, we demonstrate that Serratia marcescens (strain Db11) was significantly more lethal to Drosophila melanogaster after growth on the International Space Station than ground-based controls, but that the host immune system is not significantly altered amongst known immune genes. High-throughput sequencing of wild-type (w1118) adult hosts infected with either space or ground-reared S. marcescens revealed few changes in gene expression, with 11 genes significantly differentially expressed (q-values <0.05) and only one gene related to the immune system. This data supports the main findings of the paper, which state that both spaceflight and low-shear modeled microgravity conditions increase the virulence of this pathogen, independent of the host immune system. This data, which shows that there are no significant immune-related changes to the host when infected with space-grown sample compared to ground-grown sample, provides further evidence that there are likely phenotypic changes to the pathogen itself that is causing increased virulence in spaceflight and in low-shear modeled microgravity.
Project description:The bone loss observed in astronauts and animal models after spaceflight is attributable to alterations in the bone tissue formation that depends from the continuous remodeling through the activities of bone-resorbing osteoclasts of hematopoietic lineage and bone-forming osteoblasts of mesenchymal origin. This disease is frequent in aged people, but develops much more rapidly in space. Our experiment, selected by ESA (European Space Agency), aimed to determine how human bone marrow mesenchymal stem cells (hBMSCs) react and differentiate in real microgravity, on board the International Space Station, in approx. 2 weeks time.
Project description:The bone loss observed in astronauts and animal models after spaceflight is attributable to alterations in the bone tissue formation that depends from the continuous remodeling through the activities of bone-resorbing osteoclasts of hematopoietic lineage and bone-forming osteoblasts of mesenchymal origin. This disease is frequent in aged people, but develops much more rapidly in space. Our experiment, selected by ESA (European Space Agency), aimed to determine how human bone marrow mesenchymal stem cells (hBMSCs) react and differentiate in real microgravity, on board the International Space Station, in approx. 2 weeks time.
Project description:The bone loss observed in astronauts and animal models after spaceflight is attributable to alterations in the bone tissue formation that depends from the continuous remodeling through the activities of bone-resorbing osteoclasts of hematopoietic lineage and bone-forming osteoblasts of mesenchymal origin. This disease is frequent in aged people, but develops much more rapidly in space. Our experiment, selected by ESA (European Space Agency), aimed to determine how human bone marrow mesenchymal stem cells (hBMSCs) react and differentiate in real microgravity, on board the International Space Station, in approx. 2 weeks time.
Project description:Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) possess tremendous advantage for cardiac regeneration. However, cell survival is challenging upon cell transplantation. Since microgravity can profoundly affect cellular properties, we investigated the effect of spaceflight on hiPSC-CMs. Cardiac spheroids derived from hiPSCs were transported to the International Space Station (ISS) via the SpaceX Crew-8 mission and cultured under space microgravity for 8 days. Beating cardiac spheroids were observed on the ISS and upon successful experimentation by the astronauts in space, the live cultures were returned to Earth. These cells had normal displacement (an indicator of contraction) and Ca2+ transient parameters in 3D live cell imaging. Proteomics analysis revealed that spaceflight upregulated many proteins involved in metabolism (n=90), cellular component of mitochondrion (n=62) and regulation of proliferation (n=10). Specific metabolic pathways upregulated by spaceflight included glutathione metabolism, biosynthesis of amino acids, and pyruvate metabolism. In addition, spaceflight upregulated cellular stress response- and survival-related proteins and the AMPK signaling pathway, a master regulator of metabolism. Transcriptomic profiles indicated that spaceflight upregulated genes associated with cardiomyocyte development, and cellular components of cardiac structure and mitochondrion. Furthermore, spaceflight upregulated genes in metabolic pathways associated with cell survival such as glycerophospholipid metabolism and glycerolipid metabolism. These findings indicate that short-term exposure of the space environment to 3D hiPSC-CMs led to significant changes in protein levels and gene expression involved in cell survival and metabolism.