scholarly journals Rapid Cellular Perception of Gravitational Forces in Human Jurkat T Cells and Transduction into Gene Expression Regulation

2020 ◽  
Vol 21 (2) ◽  
pp. 514 ◽  
Author(s):  
Cora Sandra Thiel ◽  
Swantje Christoffel ◽  
Svantje Tauber ◽  
Christian Vahlensieck ◽  
Diane de Zélicourt ◽  
...  

Cellular processes are influenced in many ways by changes in gravitational force. In previous studies, we were able to demonstrate, in various cellular systems and research platforms that reactions and adaptation processes occur very rapidly after the onset of altered gravity. In this study we systematically compared differentially expressed gene transcript clusters (TCs) in human Jurkat T cells in microgravity provided by a suborbital ballistic rocket with vector-averaged gravity (vag) provided by a 2D clinostat. Additionally, we included 9× g centrifuge experiments and rigorous controls for excluding other factors of influence than gravity. We found that 11 TCs were significantly altered in 5 min of flight-induced and vector-averaged gravity. Among the annotated clusters were G3BP1, KPNB1, NUDT3, SFT2D2, and POMK. Our results revealed that less than 1% of all examined TCs show the same response in vag and flight-induced microgravity, while 38% of differentially regulated TCs identified during the hypergravity phase of the suborbital ballistic rocket flight could be verified with a 9× g ground centrifuge. In the 2D clinostat system, doing one full rotation per second, vector effects of the gravitational force are only nullified if the sensing mechanism requires 1 s or longer. Due to the fact that vag with an integration period of 1 s was not able to reproduce the results obtained in flight-induced microgravity, we conclude that the initial trigger of gene expression response to microgravity requires less than 1 s reaction time. Additionally, we discovered extensive gene expression differences caused by simple handling of the cell suspension in control experiments, which underlines the need for rigorous standardization regarding mechanical forces during cell culture experiments in general.

2003 ◽  
Vol 83 (6) ◽  
pp. 765-776 ◽  
Author(s):  
Zhaosheng Lin ◽  
G Chris Fillmore ◽  
Tae-Hyun Um ◽  
Kojo S J Elenitoba-Johnson ◽  
Megan S Lim

2008 ◽  
Vol 45 (4) ◽  
pp. 1197
Author(s):  
Eui-Young So ◽  
Jiyoung Oh ◽  
Ji-Young Jang ◽  
Jeong-Ho Kim ◽  
Choong-Eun Lee

2007 ◽  
Vol 44 (13) ◽  
pp. 3416-3426 ◽  
Author(s):  
Eui-Young So ◽  
Jiyoung Oh ◽  
Ji-Young Jang ◽  
Jeong-Ho Kim ◽  
Choong-Eun Lee

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Cora S. Thiel ◽  
Swantje Hauschild ◽  
Andreas Huge ◽  
Svantje Tauber ◽  
Beatrice A. Lauber ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1705
Author(s):  
Sukhbir Kaur ◽  
Abdel G. Elkahloun ◽  
Jennifer D. Petersen ◽  
Anush Arakelyan ◽  
Ferenc Livak ◽  
...  

T cells and endothelial cells engage in bidirectional communication that regulates angiogenesis and T cell transmigration. Extracellular vesicles (EVs) mediate intercellular communication by the transfer of bioactive molecules including RNAs. EVs produced by a given cell type are heterogeneous in their RNA content, but it is unclear how specific EV surface markers relate to their functional effects on target cells. Our previous work established that Jurkat T cell EVs bearing CD63, MHC-I, or CD47 surface markers contain distinct noncoding RNA populations. The present study reveals that CD63+ and MHC-I+ EVs from CD47-deficient Jurkat T cells are enriched in small non-coding RNAs relative to EVs from wild-type Jurkat T cells. CD47-deficient Jurkat T cells secrete more CD63+ and MHC-I+ EVs, but MHC-I+ EVs are selectively taken up more by human umbilical vein endothelial cells. Transcriptomics analysis of endothelial cells treated with CD63+ or MHC-I+ EVs showed surface marker- and CD47-dependent changes in gene expression in the target cells. Gene set enrichment analysis identified CD47-dependent, and surface marker-dependent effects of T cell EVs on VEGF and inflammatory signaling, cell cycle, and lipid and cholesterol metabolism. Thus, subsets of T cell EVs differentially regulate endothelial cell metabolism and inflammatory and angiogenic responses.


2018 ◽  
Vol 54 (10) ◽  
pp. 692-704 ◽  
Author(s):  
Rongqun Li ◽  
Aiwen Zhuang ◽  
Jiawei Ma ◽  
Lina Ji ◽  
Xiaoli Hou ◽  
...  

2021 ◽  
Vol 22 (17) ◽  
pp. 9426
Author(s):  
Christian Vahlensieck ◽  
Cora Sandra Thiel ◽  
Ye Zhang ◽  
Andreas Huge ◽  
Oliver Ullrich

The mechanisms underlying gravity perception in mammalian cells are unknown. We have recently discovered that the transcriptome of cells in the immune system, which is the most affected system during a spaceflight, responds rapidly and broadly to altered gravity. To pinpoint potential underlying mechanisms, we compared gene expression and three-dimensional (3D) chromosomal conformational changes in human Jurkat T cells during the short-term gravitational changes in parabolic flight and suborbital ballistic rocket flight experiments. We found that differential gene expression in gravity-responsive chromosomal regions, but not differentially regulated single genes, are highly conserved between different real altered gravity comparisons. These coupled gene expression effects in chromosomal regions could be explained by underlying chromatin structures. Based on a high-throughput chromatin conformation capture (Hi-C) analysis in altered gravity, we found that small chromosomes (chr16­­–22, with the exception of chr18) showed increased intra- and interchromosomal interactions in altered gravity, whereby large chromosomes showed decreased interactions. Finally, we detected a nonrandom overlap between Hi-C-identified chromosomal interacting regions and gravity-responsive chromosomal regions (GRCRs). We therefore demonstrate the first evidence that gravitational force-induced 3D chromosomal conformational changes are associated with rapid transcriptional response in human T cells. We propose a general model of cellular sensitivity to gravitational forces, where gravitational forces acting on the cellular membrane are rapidly and mechanically transduced through the cytoskeleton into the nucleus, moving chromosome territories to new conformation states and their genes into more expressive or repressive environments, finally resulting in region-specific differential gene expression.


2021 ◽  
Vol 11 ◽  
Author(s):  
Shun Zhang ◽  
Junhui Wan ◽  
Minjie Chen ◽  
Desheng Cai ◽  
Junlan Xu ◽  
...  

Tumor-infiltrating immune cells, associated with tumor progression, are promising prognostic biomarkers. However, the relationship between levels of gene expression and that of immune cell infiltration in cervical cancer prognosis is unknown. In this study, three cervical cancer gene expression microarrays (GSE6791, GSE63678 and GSE55940) were obtained from the GEO database. The IDO1 gene was identified by differentially expressed gene screening. The gene expression profiles of TCGA and GTEx databases along with comprehensive bioinformatics analysis identified that the IDO1 gene was upregulated in cervical cancer with significant difference in expression at different N stages. In addition, it was also upregulated in HPV16 positive sample. The pan-cancer analysis identified that IDO1 was highly expressed in most cancers. TIMER analysis revealed that the expression of IDO1 in CESC shows positive correlation with CD8+ T cells, CD4+ T cells, neutrophils, dendritic cells. IDO1 expression showed remarkable positive correlation with all immune cell markers except M1 macrophages. CD8+ T cell infiltration GSEA results showed that IDO1 was mainly associated with tumor immune-related signaling pathways.


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