Molecular genetic analysis of neural stem cells after space flight and simulated microgravity on earth

Han, Yilin; Zeger, Lukas; Tripathi, Rekha; Egli, Marcel; Ille, Fabian; Lockowandt, Christian; Florin, Gunnar; Atic, Edvin; Redwan, Itedale N.; Fredriksson, Robert; Kozlova, Elena N.

doi:10.1002/bit.27858

Cited by 11 publications

(10 citation statements)

References 74 publications

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“…There are reports indicating that microgravity simulated by ground-based experiments may not have the same cellular effects as space flight conditions. Han et al 44 reported that the genes associated with proliferation and survival were upregulated in mice neural crest stem cells exposed to real space, whereas cells exposed to ground-based sµg upregulated genes associated with differentiation and inflammation. However, other studies indicate similar effects on cells exposed to zero gravity and microgravity.…”

Section: Discussionmentioning

confidence: 99%

Enhanced self-renewal of human pluripotent stem cells by simulated microgravity

et al. 2022

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A systematic study on the biological effects of simulated microgravity (sµg) on human pluripotent stem cells (hPSC) is still lacking. Here, we used a fast-rotating 2-D clinostat to investigate the sµg effect on proliferation, self-renewal, and cell cycle regulation of hPSCs. We observed significant upregulation of protein translation of pluripotent transcription factors in hPSC cultured in sµg compared to cells cultured in 1g conditions. In addition to a significant increase in expression of telomere elongation genes. Differentiation experiments showed that hPSC cultured in sµg condition were less susceptible to differentiation compared to cells in 1g conditions. These results suggest that sµg enhances hPSC self-renewal. Our study revealed that sµg enhanced the cell proliferation of hPSCs by regulating the expression of cell cycle-associated kinases. RNA-seq analysis indicated that in sµg condition the expression of differentiation and development pathways are downregulated, while multiple components of the ubiquitin proteasome system are upregulated, contributing to an enhanced self-renewal of hPSCs. These effects of sµg were not replicated in human fibroblasts. Taken together, our results highlight pathways and mechanisms in hPSCs vulnerable to microgravity that imposes significant impacts on human health and performance, physiology, and cellular and molecular processes.

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Section: Discussionmentioning

confidence: 99%

Enhanced self-renewal of human pluripotent stem cells by simulated microgravity

et al. 2022

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“…Even if gene expression changes observed in real microgravity are unique, genes found to be differentially expressed in human cells that are incubated in simulated microgravity are, in many cases, altered also in real microgravity. However, this is not valid for all cell types, as observed in human neural crest stem cells cultured in real or simulated microgravity where dysregulated genes belong to markedly different pathways [131]. Generally, cells exposed both to real or simulated space conditions reported less marked gene expression changes in simulated than in space conditions, as for the superoxide dismutase (SOD) gene which resulted in a 4.1-fold upregulation in space microgravity respect to 1.2-fold in a rotating wall vessel (RWV) [99].…”

Section: Non-coding Rnas and Gene Expression Changesmentioning

confidence: 98%

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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“…Microgravity is not common in daily life, but it has a major impact on astronauts conducting space operations. Microgravity can up- or downregulate differentiation-related genes [ 70 , 71 ], which may lead to a range of related disorders in astronauts, such as bone loss [ 72 ] and cardiovascular disease [ 73 ]. In addition, simulated microgravity conditions may also disrupt the homeostasis of the immune system and lead to dynamic changes in hematopoietic stem cells (HSC) and lineage cells [ 74 ].…”

Section: Mechanical Microenvironment For Stem Cell Growthmentioning

confidence: 99%

How the mechanical microenvironment of stem cell growth affects their differentiation: a review

Zhang

Wang

2022

Stem Cell Res Ther

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Stem cell differentiation is of great interest in medical research; however, specifically and effectively regulating stem cell differentiation is still a challenge. In addition to chemical factors, physical signals are an important component of the stem cell ecotone. The mechanical microenvironment of stem cells has a huge role in stem cell differentiation. Herein, we describe the knowledge accumulated to date on the mechanical environment in which stem cells exist, which consists of various factors, including the extracellular matrix and topology, substrate stiffness, shear stress, hydrostatic pressure, tension, and microgravity. We then detail the currently known signalling pathways that stem cells use to perceive the mechanical environment, including those involving nuclear factor-kB, the nicotinic acetylcholine receptor, the piezoelectric mechanosensitive ion channel, and hypoxia-inducible factor 1α. Using this information in clinical settings to treat diseases is the goal of this research, and we describe the progress that has been made. In this review, we examined the effects of mechanical factors in the stem cell growth microenvironment on stem cell differentiation, how mechanical signals are transmitted to and function within the cell, and the influence of mechanical factors on the use of stem cells in clinical applications.

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Molecular genetic analysis of neural stem cells after space flight and simulated microgravity on earth

Cited by 11 publications

References 74 publications

Enhanced self-renewal of human pluripotent stem cells by simulated microgravity

Enhanced self-renewal of human pluripotent stem cells by simulated microgravity

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

How the mechanical microenvironment of stem cell growth affects their differentiation: a review

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