Enhanced self-renewal of human pluripotent stem cells by simulated microgravity
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ABSTRACT:
PROVIDER: PRJNA846326 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19552256_1.fastq.gz | Fastqsanger.gz | |||
| SRR19552256_2.fastq.gz | Fastqsanger.gz | |||
| SRR19552257_1.fastq.gz | Fastqsanger.gz | |||
| SRR19552257_2.fastq.gz | Fastqsanger.gz | |||
| SRR19552258_1.fastq.gz | Fastqsanger.gz |
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Project description:We developed a fast-rotating clinostat to simulate micrigravity (µg) and investigated various effects (including proliferation, self-renewal, and cell cycle regulation) of simulated microgravity (sµg) on human pluripotent stem cells (hPSC). Cells were cultured in sµg and control condition in normal gravity (1g). We observed significant upregulation of protein translation of human pluripotency transcription factors in hPSC cultured in sµg condition compared to 1g. We also noted a significant increase in the expression levels of genes involved in telomere elongation. Our induced differentiation experiments showed that hPSC cultured in sµg condition were less susceptible towards differentiation compared to cells cultured in 1g condition as indicated by the significant delayed in the process of differentiation of the cell in sµg condition. These results suggest that sµg conditions enhance the self-renewal of hPSC. Our study further revealed that sµg enhanced the cell proliferation of hPSC by regulating the expression of cell cycle associated kinases. Moreover, RNAseq analysis indicated that in sµg condition the expression of pathways related to differentiation and development and down-regulated, while multiple components of the ubiquitin proteasome system are up-regulated, thus further contributing to an enhanced self-renewal of hPSC. These effects of sµg were not replicated in human fibroblasts. Taken together, these results highlight pathways and mechanisms in hPSC vulnerable to µg that impose significant impacts on human health and performance, physiology, and cellular and molecular processes.
2022-06-11 | GSE205559 | GEO
Project description:Human exploration of outer space will inevitably require human reproduction and development in the space environment. Embryonic stem cells (ESCs) are widely employed to study mammalian development and reproduction for their characteristics of indefinite self-renewal and pluripotency. Due to the lack of experimental opportunities and related techniques, studies of the effects of microgravity on the self-renewal and differentiation of ESCs are mostly descriptive, with in-depth mechanistic studies remaining scarce. Here we show in both mouse and human ESCs that simulated microgravity (SMG)-induced stress regulates the self-renewal and pluripotency in a conserved mechanism. Specifically, SMG upregulates the expression of heat shock protein (HSP) and/or HSF1 genes, thereby increasing the expression of core pluripotency factors and the activity of the Wnt pathway. In mESCs, the upregulation of Hsps and Hsf1 genes by SMG increased the activity of the LIF/STAT3 pathway. The upregulation of Tbx3 by increased activity of the Wnt and LIF/STAT3 pathways promotes the differentiation of both mouse and human ESCs to mesendoderm under the SMG environment. Finally, the ATAC-seq and ChIP-seq analysis in this study reveal a minor effect of SMG on the global chromatin accessibility and the overall patterns of the tested histone modifications in mESCs.
2023-10-19 | E-MTAB-12390 | biostudies-arrayexpress
Project description:Human exploration of outer space will inevitably require human reproduction and development in the space environment. Embryonic stem cells (ESCs) are widely employed to study mammalian development and reproduction for their characteristics of indefinite self-renewal and pluripotency. Due to the lack of experimental opportunities and related techniques, studies of the effects of microgravity on the self-renewal and differentiation of ESCs are mostly descriptive, with in-depth mechanistic studies remaining scarce. Here we show in both mouse and human ESCs that simulated microgravity (SMG)-induced stress regulates the self-renewal and pluripotency in a conserved mechanism. Specifically, SMG upregulates the expression of heat shock protein (HSP) and/or HSF1 genes, thereby increasing the expression of core pluripotency factors and the activity of the Wnt pathway. In mESCs, the upregulation of Hsps and Hsf1 genes by SMG increased the activity of the LIF/STAT3 pathway. The upregulation of Tbx3 by increased activity of the Wnt and LIF/STAT3 pathways promotes the differentiation of both mouse and human ESCs to mesendoderm under the SMG environment. Finally, the ATAC-seq and ChIP-seq analysis in this study reveal a minor effect of SMG on the global chromatin accessibility and the overall patterns of the tested histone modifications in mESCs.
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Project description:On-demand biomanufacturing has the potential to improve healthcare and self- sufficiency during space missions. Cell-free transcription and translation reactions combined with DNA blueprints can produce promising therapeutics like bacteriophages and virus-like particles. However, how space conditions affect the synthesis and self-assembly of such complex multi- protein structures is unknown. Here, we characterize the cell-free production of infectious bacteriophage T7 virions under simulated microgravity. Rotation in a 2D-clinostat increased the number of infectious particles compared to static controls. Quantitative analyses by mass spectrometry, immuno-dot-blot and real-time PCR showed no significant differences in protein and DNA contents, suggesting enhanced self-assembly of T7 phages in simulated microgravity. While the effects of genuine space conditions on the cell-free synthesis and assembly of bacteriophages remain to be investigated, our findings support the vision of a cell-free synthesis-enabled “astropharmacy”.
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Project description:Cellular and molecular dynamics of human cells are constantly affected by gravity. Alteration of the gravitational force disturbs the cellular equilibrium, which might modify physiological and molecular characteristics. Nevertheless, biological responses of cancer cells to reduced gravitational force remains obscure. Here, we aimed to comprehend not only transcriptomic patterns but drug responses of colorectal cancer (CRC) under simulated microgravity. We established four organoids directly from CRC patients, and organoids cultured in 3D clinostat were subjected to genome wide expression profiling and drug library screening. Our observations revealed changes in cell morphology and an increase in cell viability under simulated microgravity compared to their static controls. Transcriptomic analysis highlighted a significant dysregulation in the TBC1D3 family of genes. The upregulation of cell proliferation observed under simulated microgravity conditions was further supported by enriched cell cycle processes, as evidenced by the functional clustering of mRNA expressions using cancer hallmark and gene ontology terms. Our drug screening results indicated an enhanced response rate to 5-FU under conditions of simulated microgravity, suggesting potential implications for cancer treatment strategies in simulated microgravity.
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Project description:To reveal the potential mechanisms involved in the dysfunction of antiviral immune responses under simulated microgravity conditions, we investigated the transcriptional changes related to the status of innate immune responses by RNA-seq with poly I:C or mock PBS treatment under Normal gravity or simulated microgravity conditions. Our results indicate that the retinoic acid inducible gene (RIG)-I-like receptor (RLR) and Toll-like receptor (TLR) signal pathways, which are both involved in the type-I interferon induction, are significantly inhibited by simulated microgravity effects.
2020-12-22 | GSE145967 | GEO
Project description:Simulated microgravity regulates the self-renewal and pluripotency of mouse and human embryonic stem cells - RNA-seq
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Project description:Simulated microgravity regulates the self-renewal and pluripotency of mouse and human embryonic stem cells - ChIP-seq
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Project description:Transcriptional profiling of human peripheral blood lymphocyte comparing simulated microgravity for 72 hours with untreated control. Two-condition experiment, simulated microgravity vs.untreated control. Biological replicates: 1 control, 1 treated, independently grown and harvested.
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Project description:The below table includes a smaller list of data that was analyzed by dChip and filtered by pvalue such that a file with about 4600 genes was obtained, which allowed for ease of use from 40,000 genes. Keywords: static vs simulated microgravity
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