Circulating miRNA Spaceflight Signature Reveals Targets for Countermeasure Development

Malkani, Sherina; Chin, Christopher R.; Cekanaviciute, Egle; Mortreux, Marie; Okinula, Hazeem; Tarbier, Marcel; Schreurs, Ann-Sofie; Shirazi‐Fard, Yasaman; Tahimic, Candice; Rodríguez, Deyra N.; Sexton, Brittany S.; Butler, Daniel; Verma, Akanksha; Bezdan, Daniela; Durmaz, Ceyda; MacKay, Matthew; Melnick, Ari; Meydan, Cem; Li, Sheng; Garrett-Bakelman, Francine E.; Fromm, Bastian; Afshinnekoo, Ebrahim; Langhorst, Bradley W.; Dimalanta, Eileen T.; Cheng-Campbell, Margareth; Blaber, Elizabeth A.; Schisler, Jonathan C.; Vanderburg, Charles; Friedländer, Marc R.; McDonald, J. Tyson; Costes, Sylvain V.; Rutkove, Seward B.; Grabham, Peter; Mason, Christopher E.; Beheshti, Afshin

doi:10.1016/j.celrep.2020.108448

Cited by 59 publications

(82 citation statements)

References 88 publications

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“…Together, these data suggest that HIF1A expression differs among tissues/cells, and more importantly, it is modulated by hypoxia-independent pathways. Microgravity and its analogs cause comprehensive physiological changes including autonomic imbalances, cardiac atrophy, vascular impairment and microcirculatory dysfunction, which account for cardiovascular deconditioning [49][50][51]. In this work, we revealed that several pathways involving genes showing altered rhythmicities are associated with cardiovascular deconditioning (Fig.…”

Section: Discussionmentioning

confidence: 90%

Simulated Space Environmental Factors of Weightlessness, Noise and Low Air Pressure Differentially Affect the Circadian Rhythm and Gut Microbiome

Ma¹,

Gan²,

Zhao³

et al. 2021

Preprint

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Backgroundhe circadian clock extensively regulates physiology and behavior. In space, the astronauts encounter many environmental factors that are dramatically different from those on earth, however, the effects of these factors on circadian rhythms and the mechanisms remain largely unknown. The present study aimed to investigate the changes in the mouse circadian rhythm and gut microbiome under simulated space capsule conditions, including microgravity, noise and low atmospheric pressure.ResultsNoise and low atmospheric pressure were loaded in the capsule while the conditions in the animal room remained constant. The mice in the capsule showed disturbed locomotor rhythms and faster adaptation to a 6-h phase advance. RNA sequencing of hypothalamus samples revealed that microgravity simulated by hind limb unloading (HU) and exposure to noise and low atmospheric pressure led to decreases in the quantities of differentially expressed genes (DEGs), including circadian clock genes. Changes in the rhythmicity of genes implicated in pathways of cardiovascular deconditioning and more concentrated circadian phases were found under HU or noise and low atmospheric pressure. Furthermore, 16S rRNA sequencing revealed dysbiosis in the gut microbiome, and noise and low atmospheric pressure may repress the temporal discrepancy in the microbiome community structure induced by microgravity. Changes in diel oscillation were observed in a number of gut bacteria with critical physiological consequences in metabolism and immunodefense.ConclusionsOur data demonstrate that in addition to microgravity, exposure to noise and low atmospheric pressure affect the robustness of circadian rhythms and the community structure of the gut microbiome, and these factors may interfere with each other in their adaptation to respective conditions. These findings are important to further our understanding of the alteration of circadian rhythms in the space complex environment.

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Section: Discussionmentioning

confidence: 90%

Simulated Space Environmental Factors of Weightlessness, Noise and Low Air Pressure Differentially Affect the Circadian Rhythm and Gut Microbiome

Ma¹,

Gan²,

Zhao³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Profiling miRNA expression during spaceflight has identified several miRNAs that have key regulatory roles in the cellular response to space [ 72 ]. In a recent study, Malkani et al exposed mice to spaceflight-associated conditions to evaluate the expression of known miRNAs.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Spaceflight and Microgravity on the Human Islet-1+ Cardiovascular Progenitor Cell Transcriptome

Camberos

Baio

Mandujano

et al. 2021

IJMS

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Understanding the transcriptomic impact of microgravity and the spaceflight environment is relevant for future missions in space and microgravity-based applications designed to benefit life on Earth. Here, we investigated the transcriptome of adult and neonatal cardiovascular progenitors following culture aboard the International Space Station for 30 days and compared it to the transcriptome of clonally identical cells cultured on Earth. Cardiovascular progenitors acquire a gene expression profile representative of an early-stage, dedifferentiated, stem-like state, regardless of age. Signaling pathways that support cell proliferation and survival were induced by spaceflight along with transcripts related to cell cycle re-entry, cardiovascular development, and oxidative stress. These findings contribute new insight into the multifaceted influence of reduced gravitational environments.

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“…MicroRNAs are small single strand non-coding RNA, whose functions in RNA silencing and post-transcriptional regulation of gene expression are well known. A recent milestone study identified a spaceflight-associated microRNA signature in response to simulated, shortduration and long-duration spaceflight, and simulated deep space radiation conditions [78]. In addition, the panel of spaceflight-associated microRNA has been predicted to interfere with cell signaling and metabolic pathways, partly through interaction with TGF-beta signaling [59].…”

Section: Discussionmentioning

confidence: 99%

Effect of Space Flight on the Behavior of Human Retinal Pigment Epithelial ARPE-19 Cells and Evaluation of Coenzyme Q10 Treatment

Cialdai

Bolognini

Vignali³

et al. 2021

Preprint

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Astronauts on board the International Space Station (ISS) are exposed to the damaging effects of microgravity and cosmic radiation. One of the most critical and sensitive districts of their organism is the eye, and in particular the retina, so that more than half of them develops a complex of alterations designated as Spaceflight Associated Neuro-ocular Syndrome. We explored the cellular and molecular effects induced on human retinal pigment ARPE-19 cell line by their transfer to and three days stay on board the ISS in the context of an experiment funded by the Agenzia Spaziale Italiana (ASI). Treatment of cells on board ISS with the well-known bioenergetic, antioxidant and antiapoptotic coenzyme Q10 was also evaluated. In the ground control experiment the cells were exposed to the same conditions as on the ISS, except for microgravity and radiation. Transfer of ARPE-19 retinal cells to the ISS and their living on board for three days did not impact on cell viability or apoptosis but induced cytoskeleton remodeling consisting in vimentin redistribution from the cellular boundaries to the perinuclear area, underlining the collapse of the network of intermediate vimentin filaments under unloading conditions. Morphological changes endured by ARPE-19 cells grown on board the ISS were associated with changes in the transcriptomic profile related to cellular response to space environment, and were consistent with cell dysfunction adaptations. In addition, results obtained from ARPE-19 cells treated on board ISS with coenzyme Q10 showed its potential ability to increase cell resistance to damaging insults.

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Circulating miRNA Spaceflight Signature Reveals Targets for Countermeasure Development

Cited by 59 publications

References 88 publications

Simulated Space Environmental Factors of Weightlessness, Noise and Low Air Pressure Differentially Affect the Circadian Rhythm and Gut Microbiome

Simulated Space Environmental Factors of Weightlessness, Noise and Low Air Pressure Differentially Affect the Circadian Rhythm and Gut Microbiome

The Impact of Spaceflight and Microgravity on the Human Islet-1+ Cardiovascular Progenitor Cell Transcriptome

Effect of Space Flight on the Behavior of Human Retinal Pigment Epithelial ARPE-19 Cells and Evaluation of Coenzyme Q10 Treatment

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