Microarray analysis of spaceflown murine thymus tissue reveals changes in gene expression regulating stress and glucocorticoid receptors

Lebsack, Ty W.; Fa, Vuna; Woods, Chris C.; Gruener, Raphael; Manziello, Ann; Pecaut, Michael J.; Gridley, Daila S.; Stodieck, Louis S.; Ferguson, Virginia L.; DeLuca, Dominick

doi:10.1002/jcb.22547

Cited by 51 publications

(29 citation statements)

References 62 publications

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“…Globally, all transcripts were increased in the thymus of 2G pups, except those coding for IL-7 and IL-7Rα, suggesting that hypergravity affects mainly TCR expression and signaling. The fact that IL-7 transcription is not affected at 2G is in agreement with Lebsack and colleagues28 who did not observe modifications in IL-7 expression in the thymus of space-flown mice. Woods and colleagues9 noted that simulated microgravity decreased the expression of IL-7Rα in the murine thymus.…”

Section: Discussionsupporting

confidence: 91%

Hypergravity exposure during gestation modifies the TCRβ repertoire of newborn mice

Ghislin

Ouzren-Zarhloul

Kaminski

et al. 2015

Sci Rep

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During spaceflight, organisms are subjected to mechanical force changes (gravity (G) changes) that affect the immune system. However, gravitational effects on lymphopoiesis have rarely been studied. Consequently, we investigated whether the TCRβ repertoire, created by V(D)J recombination during T lymphopoiesis, is affected by hypergravity exposure during murine development. To address this question, C57BL/6j mice were mated in a centrifuge so that embryonic development, birth and TCRβ rearrangements occurred at 2G. Pups were sacrificed at birth, and their thymus used to quantify transcripts coding for factors required for V(D)J recombination and T lymphopoiesis. We also created cDNA mini-libraries of TCRβ transcripts to study the impact of hypergravity on TCRβ diversity. Our data show that hypergravity exposure increases the transcription of TCRβ chains, and of genes whose products are involved in TCR signaling, and affects the V(D)J recombination process. We also observed that ~85% of the TCRβ repertoire is different between hypergravity and control pups. These data indicate that changing a mechanical force (the gravity) during ontogeny will likely affect host immunity because properties of loops constituting TCR antigen-binding sites are modified in hypergravity newborns. The spectrum of peptides recognized by TCR will therefore likely be different.

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Section: Discussionsupporting

confidence: 91%

Hypergravity exposure during gestation modifies the TCRβ repertoire of newborn mice

Ghislin

Ouzren-Zarhloul

Kaminski

et al. 2015

Sci Rep

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“…Heat shock proteins are highly conserved in both kingdoms, and heat shock genes are upregulated in some spaceflight studies. At least one of the subclass of heat shock genes highly induced in this study (Hsp90) is also induced in mouse thymus after exposure to spaceflight (Lebsack et al, 2010). Stress also exacerbates sensitivity to pathogen attack in both plants and animals, and there are common mechanisms for triggering an immune response, such as nitric oxide and mitogen-activated protein kinase cascades (Nurnberger et al, 2004).…”

Section: Discussionmentioning

confidence: 63%

“…Genome-wide studies of the impact of spaceflight on animal systems are slightly more common, particularly for cell lines from bone-derived cultures, mice, and drosophila models. While a full review of that literature is beyond the scope of this study, recent studies do demonstrate clear transcriptome differences during spaceflight, including studies of murine muscle ) and thymus tissue (Lebsack et al, 2010). Drosophila and Caenorhabditis elegans show six differentially expressed genes common to these two diverse species (Leandro et al, 2007;Adenle et al, 2009).…”

Section: Discussionmentioning

confidence: 92%

Spaceflight Transcriptomes: Unique Responses to a Novel Environment

Paul

Zupanska²,

Ostrow³

et al. 2012

Astrobiology

133

141

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The spaceflight environment presents unique challenges to terrestrial biology, including but not limited to the direct effects of gravity. As we near the end of the Space Shuttle era, there remain fundamental questions about the response and adaptation of plants to orbital spaceflight conditions. We address a key baseline question of whether gene expression changes are induced by the orbital environment, and then we ask whether undifferentiated cells, cells presumably lacking the typical gravity response mechanisms, perceive spaceflight. Arabidopsis seedlings and undifferentiated cultured Arabidopsis cells were launched in April, 2010, as part of the BRIC-16 flight experiment on STS-131. Biologically replicated DNA microarray and averaged RNA digital transcript profiling revealed several hundred genes in seedlings and cell cultures that were significantly affected by launch and spaceflight. The response was moderate in seedlings; only a few genes were induced by more than 7-fold, and the overall intrinsic expression level for most differentially expressed genes was low. In contrast, cell cultures displayed a more dramatic response, with dozens of genes showing this level of differential expression, a list comprised primarily of heat shock-related and stress-related genes. This baseline transcriptome profiling of seedlings and cultured cells confirms the fundamental hypothesis that survival of the spaceflight environment requires adaptive changes that are both governed and displayed by alterations in gene expression. The comparison of intact plants with cultures of undifferentiated cells confirms a second hypothesis: undifferentiated cells can detect spaceflight in the absence of specialized tissue or organized developmental structures known to detect gravity.

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“…Additionally, mRNA changes, as detected by microarray, in thymus tissue taken from mice spending 13 days aboard a space shuttle demonstrate that there is alteration in gene expression occurring as a result of combination microgravity and increased stress. These alterations include genes that are involved in regulation of stress, glucocorticoid receptor metabolism, and T cell signaling activity (36). More recently, there is evidence that hypergravity has an effect on the TCRβ diversity, demonstrating an 85% difference in TCRβ repertoire in mice born under increased gravitation force (37).…”

Section: Discussionmentioning

confidence: 99%