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

Camberos, Victor; Baio, Jonathan; Mandujano, Ana; Martinez, Aida F.; Bailey, Leonard L.; Hasaniya, Nahidh; Kearns‐Jonker, Mary

doi:10.3390/ijms22073577

Cited by 20 publications

(19 citation statements)

References 86 publications

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“…Interestingly, lifetime exposure of Drosophila to microgravity leads to diminished cardiac size, cardiac dysfunction, altered remodeling, and proteosomal abnormalities [36]. Furthermore, spaceflight causes cardiac progenitor cells in culture to display a gene expression profile consistent with early, stem-like function along with increased oxidative stress and re-entry into the cell cycle [37]. Thus, our study on expression levels of oxidative stress and cell cycle-related genes provides novel findings on how the heart responds to spaceflight at the tissue level.…”

Section: Discussionmentioning

confidence: 99%

Spaceflight Modulates the Expression of Key Oxidative Stress and Cell Cycle Related Genes in Heart

Kumar

Tahimic

Almeida

et al. 2021

IJMS

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Spaceflight causes cardiovascular changes due to microgravity-induced redistribution of body fluids and musculoskeletal unloading. Cardiac deconditioning and atrophy on Earth are associated with altered Trp53 and oxidative stress-related pathways, but the effects of spaceflight on cardiac changes at the molecular level are less understood. We tested the hypothesis that spaceflight alters the expression of key genes related to stress response pathways, which may contribute to cardiovascular deconditioning during extended spaceflight. Mice were exposed to spaceflight for 15 days or maintained on Earth (ground control). Ventricle tissue was harvested starting ~3 h post-landing. We measured expression of select genes implicated in oxidative stress pathways and Trp53 signaling by quantitative PCR. Cardiac expression levels of 37 of 168 genes tested were altered after spaceflight. Spaceflight downregulated transcription factor, Nfe2l2 (Nrf2), upregulated Nox1 and downregulated Ptgs2, suggesting a persistent increase in oxidative stress-related target genes. Spaceflight also substantially upregulated Cdkn1a (p21) and cell cycle/apoptosis-related gene Myc, and downregulated the inflammatory response gene Tnf. There were no changes in apoptosis-related genes such as Trp53. Spaceflight altered the expression of genes regulating redox balance, cell cycle and senescence in cardiac tissue of mice. Thus, spaceflight may contribute to cardiac dysfunction due to oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Spaceflight Modulates the Expression of Key Oxidative Stress and Cell Cycle Related Genes in Heart

Kumar

Tahimic

Almeida

et al. 2021

IJMS

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“…In HUVEC cells cultured for 10 days on the ISS, Versari et al [ 93 ] identified alterations in focal adhesion, over-expression of TXNIP gene, coding for the thioredoxin-interacting protein, and oxidative phosphorylation, that lead to a condition of oxidative stress that promotes DNA damage and inflammation. By transcriptomic analyses carried out in human adult and neonatal cardiovascular progenitors cultured 30 days aboard the ISS, Camberos et al [ 94 ] detected significant alterations in genes belonging to oxidative stress, with the superoxide dismutase 2 ( SOD2 ) gene significantly induced. Pathways for cell proliferation and survival, stemness, senescence, and cardiovascular development were also enriched.…”

Section: Genetic and Epigenetic Changes In Space-flown Human Cellsmentioning

confidence: 99%

Genomic Changes Driven by Radiation-Induced DNA Damage and Microgravity in Human Cells

Beheshti

McDonald

Hada

et al. 2021

IJMS

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The space environment consists of a complex mixture of different types of ionizing radiation and altered gravity that represents a threat to humans during space missions. In particular, individual radiation sensitivity is strictly related to the risk of space radiation carcinogenesis. Therefore, in view of future missions to the Moon and Mars, there is an urgent need to estimate as accurately as possible the individual risk from space exposure to improve the safety of space exploration. In this review, we survey the combined effects from the two main physical components of the space environment, ionizing radiation and microgravity, to alter the genetics and epigenetics of human cells, considering both real and simulated space conditions. Data collected from studies on human cells are discussed for their potential use to estimate individual radiation carcinogenesis risk from space exposure.

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“…Genes related to mechanotransduction were downregulated, while the expression of cytoskeletal genes and calcium signaling molecules was significantly elevated only in neonatal CPCs. Cytoskeletal organization and migration were both affected by spaceflight in neonatal and adult CPCs, however, only neonatal CPCs experienced increased expression of early developmental markers and a higher potential to proliferate (Baio et al, 2018;Camberos et al, 2019Camberos et al, , 2021. Wnorowski et al (2019) have shown that monolayers of beating cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) that were sent to the ISS for a period of 5.5 weeks, had no significant effect on the morphology.…”

Section: The Role(s) Played By Microgravity On Cardiomyocyte Functionmentioning

confidence: 99%

Microgravity × Radiation: A Space Mechanobiology Approach Toward Cardiovascular Function and Disease

Basirun

Ferlazzo

Howell

et al. 2021

Front. Cell Dev. Biol.

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In recent years, there has been an increasing interest in space exploration, supported by the accelerated technological advancements in the field. This has led to a new potential environment that humans could be exposed to in the very near future, and therefore an increasing request to evaluate the impact this may have on our body, including health risks associated with this endeavor. A critical component in regulating the human pathophysiology is represented by the cardiovascular system, which may be heavily affected in these extreme environments of microgravity and radiation. This mini review aims to identify the impact of microgravity and radiation on the cardiovascular system. Being able to understand the effect that comes with deep space explorations, including that of microgravity and space radiation, may also allow us to get a deeper understanding of the heart and ultimately our own basic physiological processes. This information may unlock new factors to consider with space exploration whilst simultaneously increasing our knowledge of the cardiovascular system and potentially associated diseases.

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

Cited by 20 publications

References 86 publications

Spaceflight Modulates the Expression of Key Oxidative Stress and Cell Cycle Related Genes in Heart

Spaceflight Modulates the Expression of Key Oxidative Stress and Cell Cycle Related Genes in Heart

Genomic Changes Driven by Radiation-Induced DNA Damage and Microgravity in Human Cells

Microgravity × Radiation: A Space Mechanobiology Approach Toward Cardiovascular Function and Disease

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