The Trends in Global Gene Expression in Mouse Embryonic Stem Cells During Spaceflight

Overview

Journal Front Genet

Date 2019 Sep 26

PMID 31552089

Citations 4

Authors

Lili An

Yanming Li

Yingjun Fan

Ning He

Fanlei Ran

Hongzhu Qu

Yanqiu Wang

Xuetong Zhao

Chen Ye

Yuanda Jiang

Xiangdong Fang

Haiying Hang

Affiliations

Soon will be listed here.

Abstract

The environment in space differs greatly from the environment on the ground. Spaceflight causes a number of physiological changes in astronauts, such as bone loss and immune system dysregulation. These effects threaten astronauts' space missions, and understanding the underlying cellular and molecular mechanisms is important to manage the risks of space missions. The biological effects of spaceflight on mammalian cells, especially with regards to DNA damage, have attracted much attention. mouse embryonic stem cells (mESCs) are known to be extremely sensitive to DNA damage agents. In this study, a project of the SJ-10 satellite programme, we investigated the gene expression profiles of both mESCs and (wild-type) mESCs in space with a focus on genes critical for inducing, preventing, or repairing genomic DNA lesions. We found that spaceflight downregulated more genes than it upregulated in both wild-type and mESCs, indicating a suppressive effect of spaceflight on global gene expression. In contrast, deletion upregulated more genes than it downregulated. Of note, spaceflight mainly affected organ development and influenced a wide range of cellular functions in mESCs, while deletion mainly affected the development and function of the hematological system, especially the development, differentiation and function of immune cells. The patterns of gene expression in mouse embryonic stem cells in space is distinct from those in other types of cells. In addition, both spaceflight and deletion downregulated DNA repair genes, suggesting a possibility that spaceflight has negative effects on genome for embryonic stem cells and the effects are likely worsen when the genome maintenance mechanism is defective.

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References

Baloh R, Enomoto H, Johnson Jr E, Milbrandt J . The GDNF family ligands and receptors - implications for neural development. Curr Opin Neurobiol. 2000; 10(1):103-10. DOI: 10.1016/s0959-4388(99)00048-3. View

Harris S, Zhang M, Kidder L, Evans G, Spelsberg T, Turner R . Effects of orbital spaceflight on human osteoblastic cell physiology and gene expression. Bone. 2000; 26(4):325-31. DOI: 10.1016/S8756-3282(00)00234-9. View

Hammond T, Benes E, OReilly K, Wolf D, Linnehan R, Taher A . Mechanical culture conditions effect gene expression: gravity-induced changes on the space shuttle. Physiol Genomics. 2000; 3(3):163-73. DOI: 10.1152/physiolgenomics.2000.3.3.163. View

White R, AVERNER M . Humans in space. Nature. 2001; 409(6823):1115-8. DOI: 10.1038/35059243. View

Simon M . Hypoxia-inducible factor and the development of stem cells of the cardiovascular system. Stem Cells. 2001; 19(4):279-86. DOI: 10.1634/stemcells.19-4-279. View

George K, Durante M, Wu H, Willingham V, Badhwar G, Cucinotta F . Chromosome aberrations in the blood lymphocytes of astronauts after space flight. Radiat Res. 2001; 156(6):731-8. DOI: 10.1667/0033-7587(2001)156[0731:caitbl]2.0.co;2. View

Hatton D, Yue Q, Dierickx J, Roullet C, Otsuka K, Watanabe M . Calcium metabolism and cardiovascular function after spaceflight. J Appl Physiol (1985). 2001; 92(1):3-12. DOI: 10.1152/jappl.2002.92.1.3. View

Hopkins K, Auerbach W, Wang X, Hande M, Hang H, Wolgemuth D . Deletion of mouse rad9 causes abnormal cellular responses to DNA damage, genomic instability, and embryonic lethality. Mol Cell Biol. 2004; 24(16):7235-48. PMC: 479733. DOI: 10.1128/MCB.24.16.7235-7248.2004. View

Lombard D, Chua K, Mostoslavsky R, Franco S, Gostissa M, Alt F . DNA repair, genome stability, and aging. Cell. 2005; 120(4):497-512. DOI: 10.1016/j.cell.2005.01.028. View

10.

Lieberman H . Rad9, an evolutionarily conserved gene with multiple functions for preserving genomic integrity. J Cell Biochem. 2005; 97(4):690-7. DOI: 10.1002/jcb.20759. View

11.

Liu Y, Wang E . Transcriptional analysis of normal human fibroblast responses to microgravity stress. Genomics Proteomics Bioinformatics. 2008; 6(1):29-41. PMC: 5054092. DOI: 10.1016/S1672-0229(08)60018-2. View

12.

Jessberger S, Aigner S, Clemenson Jr G, Toni N, Lie D, Karalay O . Cdk5 regulates accurate maturation of newborn granule cells in the adult hippocampus. PLoS Biol. 2008; 6(11):e272. PMC: 2581629. DOI: 10.1371/journal.pbio.0060272. View

13.

Allen D, Bandstra E, Harrison B, Thorng S, Stodieck L, Kostenuik P . Effects of spaceflight on murine skeletal muscle gene expression. J Appl Physiol (1985). 2008; 106(2):582-95. PMC: 2644242. DOI: 10.1152/japplphysiol.90780.2008. View

14.

Dieriks B, De Vos W, Meesen G, Van Oostveldt K, De Meyer T, Ghardi M . High content analysis of human fibroblast cell cultures after exposure to space radiation. Radiat Res. 2009; 172(4):423-36. DOI: 10.1667/RR1682.1. View

15.

Ohnishi T, Takahashi A, Nagamatsu A, Omori K, Suzuki H, Shimazu T . Detection of space radiation-induced double strand breaks as a track in cell nucleus. Biochem Biophys Res Commun. 2009; 390(3):485-8. DOI: 10.1016/j.bbrc.2009.09.114. View

16.

Crucian B, Sams C . Immune system dysregulation during spaceflight: clinical risk for exploration-class missions. J Leukoc Biol. 2009; 86(5):1017-8. DOI: 10.1189/jlb.0709500. View

17.

Monticone M, Liu Y, Pujic N, Cancedda R . Activation of nervous system development genes in bone marrow derived mesenchymal stem cells following spaceflight exposure. J Cell Biochem. 2010; 111(2):442-52. DOI: 10.1002/jcb.22765. View

18.

An L, Wang Y, Liu Y, Yang X, Liu C, Hu Z . Rad9 is required for B cell proliferation and immunoglobulin class switch recombination. J Biol Chem. 2010; 285(46):35267-73. PMC: 2975150. DOI: 10.1074/jbc.M110.161208. View

19.

Yatagai F, Honma M, Takahashi A, Omori K, Suzuki H, Shimazu T . Frozen human cells can record radiation damage accumulated during space flight: mutation induction and radioadaptation. Radiat Environ Biophys. 2010; 50(1):125-34. DOI: 10.1007/s00411-010-0348-3. View

20.

Li T, Wang Z, Zhao Y, He W, An L, Liu S . Checkpoint protein Rad9 plays an important role in nucleotide excision repair. DNA Repair (Amst). 2013; 12(4):284-92. DOI: 10.1016/j.dnarep.2013.01.006. View