Evaluation of the effects of microgravity and hypergravity on hepatic stellate cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE178831 | GEO | 2021/06/25
REPOSITORIES: GEO
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Project description:Evaluation of the effects of microgravity and hypergravity on hepatic stellate cells
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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:A combination therapy of electromagnetic fields (EMF) and simulated microgravity (SMG) has not been examined in regenerative medicine of cartilage. In the present study, a bioreactor system using extremely low-frequency EMF and SMG was applied during the chondrogenic differentiation of human mesenchymal stem cells (hMSCs). It was hypothesized that a beneficial effect of EMF regarding chondrogenesis (COL2A) could be combined with an avoiding effect of SMG regarding hypertrophy (COLXA1) of cartilage. Pellet cultures of hMSCs formed cartilaginous tissue under the addition of growth factors (FGF; TGF-β3). Pure SMG reduced COLXA1 expression but also COL2A expression of hMSCs. Pure EMF showed no gene expression changes of hMSCs during chondrogenic differentiation. Combining EMF/SMG resulted in a re-increase of COL2A but did not reach control levels. The COL2A to COLXA1 ratio of combined EMF/SMG was not significantly different from control levels. The combination therapy of EMF/SMG did not significantly improve the chondrogenic potential of hMSCs.
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Project description:Gravitational biology and its effects on cancer cells are of great interest, especially today that space is more accessible than ever. Despite advances in space research, little is known about the impact of microgravity on tumor and its biology and data from the literature are often contradictory due to different setup, experimental designs and analyzed time-points. Exploiting the Random Positioning machine we evaluated on pancreatic cancer cells the effects of long-term exposure to simulated microgravity (SMG) performing a large proteomic, lipidomic and transcriptional analysis at 1, 7 and 9 days. Results indicate that SMG affects cellular morphology through a time-dependent activation of “Regulation of actin-based motility by Rho”and “Cdc42” pathways that contribute to the dynamic actin rearrangement involved in the formation of 3D spheroidal structures and in the enhancement of epithelial-to mesenchymal transition. To support energy stress remediation and counteract massive apoptosis activation and cell proliferation inhibition, induced by SMG, tumor cells downregulate the protein translational machinery, and undergo a metabolic reprogramming orchestrated by the activation of HIF-1a and PI3K/Akt pathways. These two pathways pave the way for glucose metabolism encouraging upregulation of glycolysis, mitochondrial activity, Tri-carboxylic acid cycle and fatty acid synthesis (rather than B oxidation), suggesting a de novo synthesis of triglycerides involved in the formation of membrane lipid bilayer and signaling mediators. This metabolic plasticity, typical of cancer stem cells, is in accordance with the SMG-mediated activation of PI3K/Akt/NFkB/ERK5/IL-8 signaling axis that significantly upregulates the expression of stem-associated proteins and expansion of cancer stem cells with a more mesenchymal phenotype and improved migratory capability. Altogether, our findings clearly indicate that microgravity induces cancer cell transformation towards the acquisition of cancer stem cell-like features, with a more aggressive and metastatic potential and pave the base for future study of response to anti neoplastic drugs under simulated microgravity.
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