Microgravity‐induced hepatogenic differentiation of rBMSCs on board the SJ‐10 satellite

Lü, Dongyuan; Sun, Shan; Zhang, Fan; Luo, Chao; Zheng, Lu; Wu, Yi; Li, Ning; Zhang, Chen; Wang, Chengzhi; Chen, Qin; Long, Mian

doi:10.1096/fj.201802075r

Cited by 18 publications

(13 citation statements)

References 61 publications

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“…Tan et al [29] reported about a reduction in focal adhesions in melanoma cells exposed to s-µ g . In space on board the SJ-10 satellite, the mechanosensitive molecules β 1 -integrin, β-actin, α-tubulin, and others were elevated, whereas among others vinculin was down-regulated in bone marrow-derived mesenchymal stem cells [40]. In addition, the authors observed an accumulation of microtubules and vimentin through the altered expression and location of focal adhesion complexes [40].…”

Section: Discussionmentioning

confidence: 99%

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Real Microgravity Influences the Cytoskeleton and Focal Adhesions in Human Breast Cancer Cells

Nassef

Kopp

Wehland

et al. 2019

IJMS

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With the increasing number of spaceflights, it is crucial to understand the changes occurring in human cells exposed to real microgravity (r-µg) conditions. We tested the effect of r-µg on MCF-7 breast cancer cells with the objective to investigate cytoskeletal alterations and early changes in the gene expression of factors belonging to the cytoskeleton, extracellular matrix, focal adhesion, and cytokines. In the Technische Experimente unter Schwerelosigkeit (TEXUS) 54 rocket mission, we had the opportunity to conduct our experiment during 6 min of r-µg and focused on cytoskeletal alterations of MCF-7 breast cancer cells expressing the Lifeact-GFP marker protein for the visualization of F-actin as well as the mCherry-tubulin fusion protein using the Fluorescence Microscopy Analysis System (FLUMIAS) for fast live-cell imaging under r-µg. Moreover, in a second mission we investigated changes in RNA transcription and morphology in breast cancer cells exposed to parabolic flight (PF) maneuvers (31st Deutsches Zentrum für Luft- und Raumfahrt (DLR) PF campaign). The MCF-7 cells showed a rearrangement of the F-actin and tubulin with holes, accumulations in the tubulin network, and the appearance of filopodia- and lamellipodia-like structures in the F-actin cytoskeleton shortly after the beginning of the r-µg period. PF maneuvers induced an early up-regulation of KRT8, RDX, TIMP1, CXCL8 mRNAs, and a down-regulation of VCL after the first parabola. E-cadherin protein was significantly reduced and is involved in cell adhesion processes, and plays a significant role in tumorigenesis. Changes in the E-cadherin protein synthesis can lead to tumor progression. Pathway analyses indicate that VCL protein has an activating effect on CDH1. In conclusion, live-cell imaging visualized similar changes as those occurring in thyroid cancer cells in r-µg. This result indicates the presence of a common mechanism of gravity perception and sensation.

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Section: Discussionmentioning

confidence: 99%

“…Western blot analysis, gel electrophoresis, trans-blotting, and densitometry were carried out following routine protocols as described previously [38,39,40]. Following lysis and centrifugation, aliquots of 30 µ g were subjected to SDS-PAGE and Western blotting.…”

Section: Methodsmentioning

confidence: 99%

Real Microgravity Influences the Cytoskeleton and Focal Adhesions in Human Breast Cancer Cells

Nassef

Kopp

Wehland

et al. 2019

IJMS

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“…Moreover, the number of hMSCs with a disordered actin cytoskeleton gradually increased and the cells showed a contracted phenotype [85,86]. Besides, in rat MSCs on board the SJ-10 Satellite, the expression of VCAM1, ICAM1, CD44, and vinculin was reduced along with depolymerization of actin filaments and the accumulation of microtubules due to true weightlessness in space [87]. With experiments in vitro and in vivo, it was demonstrated that redistribution of vinculin also occurred in hMSCs after 6 h of simulated microgravity [85], and the number of vinculin-containing focal adhesions was decreased in rat MSCs after 28 days of HLU [88].…”

Section: Microgravity Regulates Adhesion and Fate Determination Of Stem Cellsmentioning

confidence: 99%

“…Beyond that, other researchers have demonstrated that although microgravity destroys the adhesion ability of stem cells, it can also drive cell differentiation and transdifferentiation. Lu et al demonstrated that space microgravity not only reduces adhesion molecule expression but also promote the hepatogenic differentiation of MSCs [87]. The upregulation of hepatocyte-specific cytokeratin 18 and albumin makes cell mature [87].…”

Section: Microgravity Regulates Adhesion and Fate Determination Of Stem Cellsmentioning

confidence: 99%

The Impact of Spaceflight and Simulated Microgravity on Cell Adhesion

Lin

Zhang

Wei

et al. 2020

IJMS

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Microgravity induces a number of significant physiological changes in the cardiovascular, nervous, immune systems, as well as the bone tissue of astronauts. Changes in cell adhesion properties are one aspect affected during long-term spaceflights in mammalian cells. Cellular adhesion behaviors can be divided into cell–cell and cell–matrix adhesion. These behaviors trigger cell–cell recognition, conjugation, migration, cytoskeletal rearrangement, and signal transduction. Cellular adhesion molecule (CAM) is a general term for macromolecules that mediate the contact and binding between cells or between cells and the extracellular matrix (ECM). In this review, we summarize the four major classes of adhesion molecules that regulate cell adhesion, including integrins, immunoglobulin superfamily (Ig-SF), cadherins, and selectin. Moreover, we discuss the effects of spaceflight and simulated microgravity on the adhesion of endothelial cells, immune cells, tumor cells, stem cells, osteoblasts, muscle cells, and other types of cells. Further studies on the effects of microgravity on cell adhesion and the corresponding physiological behaviors may help increase the safety and improve the health of astronauts in space.

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“…In recent studies, we subjected thyroid and breast cancer cells and endothelial cells, which had been cultured for a few days on ground, in Space or on a Random Positioning Machine (RPM) simulating microgravity, to mass spectrometry or microarray gene analyses. These high throughput omics technologies unveiled thousands of proteins or genes [5][6][7][8], including gravity-sensitive cell adhesion proteins such as integrins, which form alpha-beta dimers [9,10], cadherins [6,11,12], and other cell adhesion molecules [13][14][15] as well as CD44 [16], whose sensitivity to microgravity has repeatedly been described [17]. CD44 is a cell surface receptor that plays a role in cell-cell interactions, cell adhesion, and migration, helping the cells to sense and respond to changes in the tissue microenvironment [18,19].…”

Section: Introductionmentioning

confidence: 99%

Insight in Adhesion Protein Sialylation and Microgravity Dependent Cell Adhesion—An Omics Network Approach

Bauer

Gombocz²,

Wehland

et al. 2020

IJMS

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The adhesion behavior of human tissue cells changes in vitro, when gravity forces affecting these cells are modified. To understand the mechanisms underlying these changes, proteins involved in cell-cell or cell-extracellular matrix adhesion, their expression, accumulation, localization, and posttranslational modification (PTM) regarding changes during exposure to microgravity were investigated. As the sialylation of adhesion proteins is influencing cell adhesion on Earth in vitro and in vivo, we analyzed the sialylation of cell adhesion molecules detected by omics studies on cells, which change their adhesion behavior when exposed to microgravity. Using a knowledge graph created from experimental omics data and semantic searches across several reference databases, we studied the sialylation of adhesion proteins glycosylated at their extracellular domains with regards to its sensitivity to microgravity. This way, experimental omics data networked with the current knowledge about the binding of sialic acids to cell adhesion proteins, its regulation, and interactions in between those proteins provided insights into the mechanisms behind our experimental findings, suggesting that balancing the sialylation against the de-sialylation of the terminal ends of the adhesion proteins’ glycans influences their binding activity. This sheds light on the transition from two- to three-dimensional growth observed in microgravity, mirroring cell migration and cancer metastasis in vivo.

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Microgravity‐induced hepatogenic differentiation of rBMSCs on board the SJ‐10 satellite

Cited by 18 publications

References 61 publications

Real Microgravity Influences the Cytoskeleton and Focal Adhesions in Human Breast Cancer Cells

Real Microgravity Influences the Cytoskeleton and Focal Adhesions in Human Breast Cancer Cells

The Impact of Spaceflight and Simulated Microgravity on Cell Adhesion

Insight in Adhesion Protein Sialylation and Microgravity Dependent Cell Adhesion—An Omics Network Approach

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