MicroRNA Expression Profiles in Cultured Human Fibroblasts in Space (Micro-7) - 07.11.18

Overview | Description | Applications | Operations | Results | Publications | Imagery

ISS Science for Everyone

Science Objectives for Everyone
The majority of cells in the human body are non-dividing cells that provide critical functions, from blood cells, to cells in different organs. Micro-7 studies how microgravity affects the genetic expression and physical shape of these types of cells for the first time. Understanding how these cells function in microgravity is a step toward understanding how organs, tissues, and the entire body change during spaceflight.
Science Results for Everyone
Now that is high culture. This experiment looks at when, in their life cycle, cultured cells undergo genetic changes caused by microgravity.  Genetic changes in cells were seen early in flight, due mainly to cell growth, as a result of being in the microgravity environment. By day 14 in space, gene expression profiles and cell structure were the same in flight and ground samples.  Cultured cells seem to multiply faster in space, suggesting microgravity does not inhibit free growth. 

The following content was provided by Kevin Sato, Ph.D., and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom: N/A

Principal Investigator(s)
Honglu Wu, Ph.D., NASA Johnson Space Center, Houston, TX, United States

Ye Zhang, Ph.D., NASA Kennedy Space Center, Cape Canaveral, FL, United States

NASA Ames Research Center, Moffett Field, CA, United States
BioServe Space Technologies, Boulder, CO, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
Human Exploration and Operations Mission Directorate (HEOMD)

Research Benefits
Information Pending

ISS Expedition Duration
March 2014 - September 2014

Expeditions Assigned

Previous Missions
Information Pending

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Experiment Description

Research Overview

  • It is not known how the space flight environment affects non-dividing cells, which are the majority of cells that make up the human body.  Changes are observed to organs, tissues and whole body systems, yet the root causes are not understood or known.  In order to gain insight, it is important to study the fundamental functional unit of tissues and organs, which is the cell.   By studying a single cell type in culture instead of whole tissues or organs, the scientist will be able to clearly investigate the root molecular and cellular biological effects of the space flight environment on the cell and eliminate potential complicating factors due to different cell types that may make up a specific tissue type or organ. The bleomycin study will examine the induction of, as well as cellular responses to, DNA double strand breaks (DSB) in the microgravity environment. Living organisms in space are constantly exposed to space radiation and other environmental toxins. Differences in the capability to repair or misrepair DNA damages between the microG and 1G conditions will impact the accuracy of the risk assessment of astronauts, and the accuracy in predicting the mutation rate in microorganisms.  

  • The data from this study will provide deeper insight into how gene expression regulates cellular adaptation to the space flight environment.  Specifically, it will provide further understanding of the roles microRNA (miRNA) play in gene expression regulation that will be of benefit to both space flight exploration and Earth scientific research.

  • The identification of the role of miRNA in gene regulation will help to elucidate the fundamental process that are affect by or regulate adaptation to the space flight environment. Since this experiment compares space flight samples with ground samples, differences between the the specimens will elucidate unknown functions of miRNA and identification of cellular/biochemical pathways that are regulated by miRNAs. Also, since the experiment uses normal human fibroblast in their non-dividing condition, it will provide new information on how normal cellular function and adaptation are affected by the space environment.  Collectively, the data may be used for Earth-based fundamental and biomedical research to examine if the changes observed in space flight are seen in disease states of tissues and organs.  Furthermore, the data may point out important targets for further study in ground-based and space-based research.  Ultimately, the data may be applied to understanding tissue and organ structural maintenance and disease.

1) Determine miRNA expression profiles in confluent AG1522 human fibroblast cells in space and on the ground with PCR array.
2) Determine gene expression profiles in confluent AG1522 human fibroblast cells in space and on the ground with Illumina gene array.
3) Determine changes in miRNA and gene expression profiles in and pathways affected by the microgravity environment using statistical and bioinformatics methodologies.  Determine correlation between miRNA and RNA expression patterns.
4) Measure the number of DSB in the cultures used for the Bleomycin study plus 1-3 above.

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Space Applications
Human tissues and organs are made of non-dividing but functional cells. According to Earth-based experiments, non-dividing cells’ genetic expression and micro-RNA profiles change in response to simulated microgravity. Micro-7 is the first space experiment to directly investigate how microgravity affects the gene expression and physical shape of fibroblasts, which are common tissue cells. Fibroblasts are critical for wound healing and tissue structure, so understanding how they function in space could provide crucial insight for future space missions.

Earth Applications
Understanding the differences between cells’ genetic expression on the ground and in microgravity can provide new insights into genetic regulation and signaling pathways. Micro-7 aims to explain the role of micro-RNA, a type of molecule involved in how genetic information is processed in a cell. Micro-RNA might be important in regulating how cells respond to the space environment, and data from Micro-7 could be compared with ground-based data to provide insight into miRNA’s role in gene regulation. Understanding fundamental molecular processes in cells could provide new pathways for disease treatment, including potential new pharmaceutical products.

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Operational Requirements and Protocols

See previous sections listing requirements.

The crew will inject a preservative or fixative into the biochamber at specific time points.  After the specimens are processed, the biochambers will be transferred to either +4 oC or -80 oC stowage.  If the CGBA will be powered for return, the +4 oC stowed specimens may be returned to the CGBA for return, otherwise the specimens will be transferred to a +4 oC cold stowage bag.  The cryo (if needed) specimens will be transferred to either GLACIER or a cryo-cold stowage bag for return.  

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Decadal Survey Recommendations

Information Pending

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Results/More Information

Microgravity is a significant stressor experienced by living organisms during space flight and has been shown to influence gene expression patterns and protein levels in lab-grown cells.  Early space studies with human fibroblasts (cells in connective tissue) identified genes whose expression was modified as a result of space flight.  The Micro-7 investigation has examined the responses of human fibroblasts cultured in space for 3 and 14 days, respectively, to investigate changes in gene and microRNA (miRNA) expressions.  Results of the experiment showed that on day 3, both the flown and ground cells were still growing slowly and the genetic changes seen with these cells were space induced.  On day 14, when the cells were in a non-dividing resting state, the gene and miRNA expression profile of the flight sample was indistinguishable from that of the ground sample.  Analysis of cytoskeletal changes (filaments and tubules within the cell) showed no difference between the flown and ground samples.  Although the cells seemed to multiply faster in space than they did on the ground, data suggest that in true non-dividing human fibroblasts in culture, microgravity has little effect on their gene and miRNA expressions.
A second objective of Micro-7 was to examine the cellular responses in space to DNA damage induced by space radiation or toxic chemicals. In space, fibroblasts were treated with bleomycin which caused DNA damage. Cells in flown and ground samples did not differ significantly in their response to such damage, as quantified by a DNA damage marker and expressions of DNA damage response genes. A third objective of Micro-7 was to detect damage in human fibroblasts from direct exposure to cosmic radiation. Understanding how space radiation affects cells is critical for the health of the astronauts during future space exploration missions. Image analysis of a DNA damage marker were captured with a laser confocal microscope to determine size and volume. Quantitative analysis of results showed several larger DNA damage signals displaying a track pattern in flown cells on day 14. These results suggest only a small fraction of large size signals can be attributed to space radiation exposure.

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Results Publications

    Zhang Y, Lu T, Wong M, Wang X, Stodieck LS, Karouia F, Story M, Wu H.  Transient gene and microRNA expression profile changes of confluent human fibroblast cells in spaceflight. FASEB: Federation of American Societies for Experimental Biology Journal. 2016 February 25; epub: fj.201500121. DOI: 10.1096/fj.201500121. PMID: 26917741.

    Lu T, Zhang Y, Wong M, Feiveson AH, Gaza R, Stoffle NN, Wang H, Wilson B, Rohde L, Stodieck LS, Karouia F, Wu H.  Detection of DNA damage by space radiation in human fibroblasts flown on the International Space Station. Life Sciences in Space Research. 2017 February; 12: 24-31. DOI: 10.1016/j.lssr.2016.12.004.

    Lu T, Zhang Y, Kidane Y, Feiveson AH, Stodieck LS, Karouia F, Ramesh GT, Rohde L, Wu H.  Cellular responses and gene expression profile changes due to bleomycin-induced DNA damage in human fibroblasts in space. PLOS ONE. 2017 March 1; 12(3): e0170358. DOI: 10.1371/journal.pone.0170358.

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Ground Based Results Publications

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ISS Patents

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Related Publications

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Related Websites

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Confluent tissue culture of human skin fibroblasts. Photo courtesy of BioServe Space Technologies at the University of Colorado.

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 BioServe CGBA incubator  Photo courtesy of BioServe Space Technologies at the University of Colorado.

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image NASA Image: ISS039E015593 - NASA astronaut Rick Mastracchio processes a Micro-7 BioCell Habitat with use of a Fixation Kit.
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image NASA Image: ISS039E015644 - NASA astronaut Rick Mastracchio processes a Micro-7 BioCell Habitat with use of a Fixation Kit.
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image NASA Image: ISS039E018752 - NASA astronaut Rick Mastracchio processes a Micro-7 BioCell Habitat with use of a Fixation Kit.
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