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BDE-47 CpG Methylomic Alterations in Human Embryonic Stem Cell-derived Neural Precursor Cells

ABSTRACT: BDE-47 CpG Methylomic Alterations in Human Embryonic Stem Cell-derived Neural Precursor Cells

PROVIDER: PRJNA516438 | ENA |

REPOSITORIES: ENA

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BDE-47 CpG Methylomic Alterations in Human Embryonic Stem Cell-derived Neural Precursor Cells

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Methylomic Profiling of BDE-47 Effects on Human Placental Cytotrophoblasts

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BDE-47 Transcriptomic Alterations in Human Primary Villous Cytrophoblasts

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Transcriptomic analysis of HepG2 cells treated with BDE-47, BDE-99, BDE-209 and their ternary mixture at 1nM as a dietary relevant concentration

Project description:Polybrominated diphenyl ethers (PBDEs) are persistent organic chemicals implied as flame re-tardants. Humans are mainly exposed to BDE-47, -99 and -209 congeners by diet. PBDEs are metabolic disruptors with liver as main target organ. To investigate their mode of action at a human relevant concentration, we exposed HepG2 cells to these congeners and their mixture at 1 nM for 72h, analyzing their transcriptomic and proteomic profiles. KEGG pathways and GSEA Hallmarks enrichment analyses evidenced that BDE-47 disrupted the glucose metabolism and Hypoxia pathway; all the congeners and the MIX affected lipid metabolism and signaling Hallmarks regulating metabolism as mTORC1 and PI3K/AKT/MTOR. These results were confirmed by glucose secretion depletion and increased lipid accumulation, especially in BDE-47 and -209 treated cells. These congeners also affected the EGFR/MAPK signaling; further, BDE-47 enriched the Estrogen pathway. Interestingly, BDE-209 and the MIX increased ERα gene expression, whereas all the congeners and the MIX induced ERβ and PPARγ. We also found that PBDEs modulated several lncRNAs and that HNRNAP1 represented a central hub in all the four interaction networks. Overall, despite the low concentration used, the PBDEs investigated affected glucose and lipid metabolism with different underlying modes of action, as highlighted by the integrated omics analysis. These results may support the mechanism-based risk assessment of these compounds in relation to liver metabolism disruption.

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Transcriptome profiling analysis of Mactra veneriformis exposed to BDE-47 by deep sequencing

Project description:RNA-seq provided a general overview of the gene expression profiles of the digestive glands of Mactra veneriformis exposed to 2, 2′,4,4′-tetrabromodiphenyl ether (BDE-47, a type of widely used brominated flame retardants).

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BDE-47 Transcriptomic Alterations in Human Embryonic Stem Cell-derived Neural Precursor Cells

Project description:BDE-47 Transcriptomic Alterations in Human Embryonic Stem Cell-derived Neural Precursor Cells

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Transcriptomic Analysis of Gonadal Adipose Tissue in Male Mice Exposed Perinatally to 2,2',4,4'- Tetrabromodiphenyl Ether (BDE-47)

Project description:For the majority of lipophilic compounds adipose tissue is traditionally considered as storage depot and only rarely as a target organ. Meanwhile, abnormalities in adipose tissue physiology induced by chemical exposures may contribute to the current epidemic of obesity and metabolic diseases. Polybrominated diphenyl ethers (PBDEs) is a group of lipophilic flame retardants found in majority of human samples in North America. Their ability to alter physiology of adipose tissue is unknown. We exposed pregnant mice to 0.2 mg/kg body weight/day of BDE-47 perinatally. Transcriptomic changes in gonadal adipose tissue were analyzed in male offspring using RNA-seq approach with subsequent bioinformatic analysis. Genes of coagulation and complement cascade, de novo lipogenesis, and xenobiotic metabolism were altered in expression in response to BDE-47 exposure. The affected molecular network included the following hubs: PPARα, HNF1A and HNF4. These findings suggest that adipose tissue should be considered a target tissue for BDE-47, in addition to its role as a storage depot. This study also builds a background for a targeted search of sensitive phenotypic endpoints of BDE-47 exposure, including lipid profile parameters and coagulation factors in circulation. Additional studies are needed to investigate the role of PBDEs as an obesogen.

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