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T Cell Transcriptome Alterations in Healthy Volunteers Exposed to Three Weeks of Simulated Microgravity

ABSTRACT: Impairment or reduction of lymphocyte-mediated immune response has been observed during space flight or in microgravity simulation conditions, with the underlying mechanisms remaining unclear. T lymphocytes (T cells) play a critical role in human immune response. The immunosuppression encountered by humans in microgravity may be linked to its impact on T cell global transcriptome networks, affecting immune cell-cell interactions. This study involved a unique three-week microgravity simulation conducted with ten healthy male volunteers aged 25-40 using a dry immersion facility. The research aimed to explore the normal responses of the human body to long-term simulated microgravity (SMG) without any specific countermeasures implemented. To investigate the T cell response to SMG, total RNA isolated from T lymphocytes at different time points during the course of SMG was subjected to RNA sequencing. Bioinformatic analysis revealed the impact of SMG on multiple cell signaling pathways, influenced by key regulators that modulated the expression of different genes. The discovery of potential biomarker genes in T cells may offer valuable insights into studying human responses to microgravity, however, further validation of these findings in space is required.

ORGANISM(S): Homo sapiens

PROVIDER: GSE301964 | GEO | 2025/12/09

REPOSITORIES: GEO

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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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T Cell Transcriptome Alterations in Healthy Volunteers Exposed to Three Weeks of Simulated Microgravity

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