Transient gene and microRNA expression profile changes of confluent human fibroblast cells in spaceflight

Ye Zhang; Tao Lu; Michael Wong; Xiaoyu Wang; Louis Stodieck; Fathi Karouia; Michael Story; Honglu Wu

doi:10.1096/fj.201500121

Transient gene and microRNA expression profile changes of confluent human fibroblast cells in spaceflight

FASEB J. 2016 Jun;30(6):2211-24. doi: 10.1096/fj.201500121. Epub 2016 Feb 25.

Authors

Ye Zhang¹, Tao Lu², Michael Wong³, Xiaoyu Wang⁴, Louis Stodieck⁵, Fathi Karouia⁶, Michael Story⁴, Honglu Wu⁷

Affiliations

¹ Johnson Space Center, National Aeronautics and Space Administration (NASA), Houston, Texas, USA; Wyle Laboratories, Houston, Texas, USA; Kennedy Space Center, NASA, Cape Canaveral, Florida, USA;
² Johnson Space Center, National Aeronautics and Space Administration (NASA), Houston, Texas, USA; University of Houston Clear Lake, Houston, Texas, USA;
³ Johnson Space Center, National Aeronautics and Space Administration (NASA), Houston, Texas, USA;
⁴ University of Texas Southwestern Medical Center, Dallas, Texas, USA;
⁵ BioServe Space Technologies, Boulder, Colorado, USA;
⁶ Ames Research Center, NASA, Moffett Field, California, USA; and University of California San Francisco, San Francisco, California, USA.
⁷ Johnson Space Center, National Aeronautics and Space Administration (NASA), Houston, Texas, USA; honglu.wu-1@nasa.gov.

PMID: 26917741
DOI: 10.1096/fj.201500121

Abstract

Microgravity, or an altered gravity environment different from the 1 g of the Earth, has been shown to influence global gene expression patterns and protein levels in cultured cells. However, most of the reported studies that have been conducted in space or by using simulated microgravity on the ground have focused on the growth or differentiation of these cells. It has not been specifically addressed whether nonproliferating cultured cells will sense the presence of microgravity in space. In an experiment conducted onboard the International Space Station, confluent human fibroblast cells were fixed after being cultured in space for 3 and 14 d, respectively, to investigate changes in gene and microRNA (miRNA) expression profiles in these cells. Results of the experiment showed that on d 3, both the flown and ground cells were still proliferating slowly, as measured by the percentage of Ki-67(+) cells. Gene and miRNA expression data indicated activation of NF-κB and other growth-related pathways that involve hepatocyte growth factor and VEGF as well as the down-regulation of the Let-7 miRNA family. On d 14, when the cells were mostly nonproliferating, the gene and miRNA expression profile of the flight sample was indistinguishable from that of the ground sample. Comparison of gene and miRNA expressions in the d 3 samples, with respect to d 14, revealed that most of the changes observed on d 3 were related to cell growth for both the flown and ground cells. Analysis of cytoskeletal changes via immunohistochemistry staining of the cells with antibodies for α-tubulin and fibronectin showed no difference between the flown and ground samples. Taken together, our study suggests that in true nondividing human fibroblast cells in culture, microgravity experienced in space has little effect on gene and miRNA expression profiles.-Zhang, Y., Lu, T., Wong, M., Wang, X., Stodieck, L., Karouia, F., Story, M., Wu, H. Transient gene and microRNA expression profile changes of confluent human fibroblast cells in spaceflight.

Keywords: cell growth condition; microgravity; omics.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Cytoskeleton / physiology
Fibroblasts / metabolism*
Humans
MicroRNAs / genetics
MicroRNAs / metabolism*
Space Flight*
Time Factors
Transcriptome*
Weightlessness

Substances

MicroRNAs