Astronauts plasma-derived exosomes induced gene expression in AC16 cells
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ABSTRACT:
PROVIDER: PRJNA814629 | ENA |
REPOSITORIES: ENA
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Project description:There are unique stressors in the spaceflight environment. Exposure to such stressors is associated with adverse effects on astronauts' health, including increased cancer and cardiovascular disease risks. Small extracellular vesicles (sEVs, i.e., exosomes) play a vital role in intercellular communication and regulate various biological processes contributing to their role in disease pathogenesis. To assess whether spaceflight alters sEVs transcriptome profile, sEVs were isolated from the blood plasma of 3 astronauts at two different time points: 10 days before launch (L-10) and 3 days after return (R+3) from the Shuttle mission. Human adult ventricular cardiomyocyte cells (AC16) were treated with L-10 and R+3 astronauts-derived exosomes for 24 hours. Total RNA was isolated and analyzed for gene expression profiling using Affymetrix microarrays. Enrichment analysis was performed using Enrichr. Transcription factor enrichment analysis using the ENCODE/ChEA Consensus TF database identified gene sets related to the polycomb repressive complex 2 (PRC2) and Vitamin D receptor (VDR) in AC16 cells treated with R+3 compared to cells treated with L-10 astronauts-derived exosomes. Further analysis of the histone modifications using datasets from the Roadmap Epigenomics Project confirmed enrichment in gene sets related to the H3K27me3 repressive mark. Interestingly, analysis of previously published H3K27me3–chromatin immunoprecipitation sequencing (ChIP-Seq) ENCODE datasets showed enrichment of H3K27me3 in the VDR promoter. Collectively, our results suggest that astronaut-derived sEVs may epigenetically repress the expression of the VDR in human adult cardiomyocytes c by promoting the activation of the PRC2 complex and H3K27me3 levels.
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Project description:Astronauts plasma-derived exosomes induced gene expression in AC16 cells
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Project description:Ionizing radiation (IR) therapy for malignant tumors can damage adjacent tissues, leading to severe wound complications. Plasma-derived exosome treatment has recently emerged as a safe and impactful cell-free therapy. Herein, we aimed to determine whether plasma-derived exosomes could improve the healing of post-radiation wound. Rat plasma-derived exosomes (RP-Exos) were locally injected on cutaneous wounds created on the backs of irradiated rats and boosted the healing process as well as the deposition and remodeling of the extracellular matrix with collagen formation. Subsequently, the effects of RP-Exos were further evaluated on irradiated fibroblasts in vitro. The results suggested that exosomes promoted fibroblast proliferation, migration, cell cycle progression, and cell survival. Moreover, transcriptome sequencing, analysis, and quantitative polymerase chain reaction validation were performed to identify the underlying molecular mechanisms. RP-Exos enhanced the expression of cell proliferation and radioresistance-related genes, and yet downregulated ferroptosis pathway in irradiated fibroblasts. Inhibition of ferroptosis by RP-Exos was further confirmed through colorimetric assay, fluorescence probe and flow cytometry in ferroptosis-induced fibroblasts. Our results suggest that RP-Exos regulate cell proliferation and ferroptosis in radiated fibroblasts, thereby boosting the healing of radiated wounds. These findings support plasma-derived exosomes as a potential therapeutic method for post-radiation wound complications.
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Project description:Cardiac myxoma (CM) is an important aetiology of stroke in young adults, and its diagnosis is difficult in patients having stroke because of the lack of diagnostic biomarkers. Tumour-derived exosomes play a crucial role in tumour growth, metastasis, and immune regulation, and monitor disease development. We established an RNA-sequencing dataset for long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) in the plasma and tumour-derived exosomes from four patients with cardiac myxoma-related ischaemic stroke (CM-IS) and six patients with cardiac myxoma without ischaemic stroke (non-IS CM). Clean data (15.48 Gb) were obtained for lncRNAs and mRNAs. Moreover, 5,533 lncRNAs, 1,331 known miRNAs, and 412 new miRNAs were identified. Finally, gene expression profiles and differentially expressed genes were analysed in 20 samples. In the plasma samples, 74 miRNAs, 12 lncRNAs, and 693 mRNAs were identified. Tumour-derived tissue samples contained 61 miRNAs, 67 lncRNAs, and 433 mRNAs. This dataset provides a significant resource for relevant researchers to explore the potential dysregulated lncRNAs, miRNAs, and mRNAs of plasma and tumour-derived exosomes in CM-IS versus CM without stroke.
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