Project description:Identification of gravisensitive miRNAs expression in rat soleus muscle exposed to 7 and 14 days of Hindlimb suspension (HS) simulated microgravity. Microgravity causes muscle atrophy possibly due to muscle wasting overtake regeneration. Results provide insight into the molecular mechanisms regulating muscle atrophy. The expression of 23 out of 174 miRNAs was found to change at least 2-fold of 7 and/or 14 days of TS. By using real-time PCR assays, we verified the microarray data using some of the expected genes.
Project description:In space, multiple unique environmental factors, particularly microgravity and space radiation, pose constant threat to the astronaut’s health. To gain insight into the role of miRNAs and lncRNAs in response to radiation and microgravity, we analyzed RNA expression profiles in human lymphoblastoid TK6 cells incubated for 24 h in static condition or in rotating condition to stimulate microgravity in space after 2 Gy γ-ray irradiation. Expression of 14 lncRNAs and 17 mRNAs was found to be significantly down-regulated in the simulated microgravity condition. In contrast, irradiation up-regulated the expression of 55 lncRNAs and 56 mRNAs, while only one lncRNA, but no mRNA, was down-regulated. Furthermore, 2 miRNAs, 70 lncRNAs, and 87 mRNAs showed significantly altered expression under simulated microgravity after irradiation, and these changes were independently induced by irradiation and simulated microgravity. Together, our results indicate that simulated microgravity and irradiation additively and independently alter the expression of RNAs and their target genes in human lymphoblastoid cells.
Project description:Cellular and molecular dynamics of human cells are constantly affected by gravity. Alteration of the gravitational force disturbs the cellular equilibrium, which might modify physiological and molecular characteristics. Nevertheless, biological responses of cancer cells to reduced gravitational force remains obscure. Here, we aimed to comprehend not only transcriptomic patterns but drug responses of colorectal cancer (CRC) under simulated microgravity. We established four organoids directly from CRC patients, and organoids cultured in 3D clinostat were subjected to genome wide expression profiling and drug library screening. Our observations revealed changes in cell morphology and an increase in cell viability under simulated microgravity compared to their static controls. Transcriptomic analysis highlighted a significant dysregulation in the TBC1D3 family of genes. The upregulation of cell proliferation observed under simulated microgravity conditions was further supported by enriched cell cycle processes, as evidenced by the functional clustering of mRNA expressions using cancer hallmark and gene ontology terms. Our drug screening results indicated an enhanced response rate to 5-FU under conditions of simulated microgravity, suggesting potential implications for cancer treatment strategies in simulated microgravity.
Project description:Identification of gravisensitive gene expression in rat soleus muscle exposed to 7 and 14 days of Hindlimb suspension (HS) simulated microgravity. Microgravity causes muscle atrophy possibly due to muscle wasting overtake regeneration. Results provide insight into the molecular mechanisms regulating muscle atrophy. The expression of 787 (373 upregulated and 414 downregulated) and 923 (491 upregulated and 432 downregulated) genes out of 28000 was altered respectively at least 2-fold of 7 and 14 days TS, which represented 397 (233 upregulated and 164 downregulated) genes of common alteration. By using real-time PCR assays, we verified the microarray data using some of the expected genes.
Project description:Microgravity is known to affect the organization of the cytoskeleton, cell and nuclear morphology and to elicit differential expression of genes associated with the cytoskeleton, focal adhesions and the extracellular matrix. Although the nucleus is mechanically connected to the cytoskeleton through the LInker of Nucleoskeleton and Cytoskeleton (LINC) complex, the role of this group of proteins in these responses to microgravity has yet to be defined. Therefore, we used simulated microgravity achieved by growing cells on a 3d clinostat to investigate whether the LINC complex acts to mediate responses to the microgravity environment. We show that nuclear shape and differential gene expression are both responsive to simulated microgravity in a LINC-dependent manner and that this response changes with the duration of exposure to simulated microgravity. These LINC-dependent genes likely represent elements normally regulated by the mechanical forces imposed by gravity on Earth.
Project description:A multidisciplinary approach was employed to characterize morphological, biochemical and molecular changes underlying the human BMSCs response to simulated microgravity exposure during osteogenic differentiation.
Project description:Astronauts have been previously shown to exhibit decreased salivary lysozyme and increased dental calculus and gingival inflammation in response to space flight, host factors that could contribute to oral diseases such as caries and periodontitis. However, the specific physiological response of caries-causing bacteria such as Streptococcus mutans to space flight and/or ground-based simulated microgravity has not been extensively investigated. In this study, High Aspect Ratio Vessel (HARV) S. mutans simulated microgravity and normal gravity cultures were assessed for changes in metabolite and transcriptome profiles, H2O2 resistance, and competence in sucrose-containing biofilm media. Stationary phase S. mutans simulated microgravity cultures displayed increased killing by H2O2 compared to normal gravity control cultures, but competence was not affected. RNA-seq analysis revealed that expression of 153 genes was up-regulated ≥ 2-fold and 94 genes down-regulated ≥ 2-fold during simulated microgravity HARV growth. These included a number of genes located on extrachromosomal elements, as well as genes involved in carbohydrate metabolism, translation, and stress responses. Collectively, these results suggest that growth under microgravity analog conditions promotes changes in S. mutans gene expression and physiology that may translate to an altered cariogenic potential of this organism during space flight missions.