Persistent organic pollutants alter DNA methylation during human adipocyte differentiation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE75133 | GEO | 2016/12/27
SECONDARY ACCESSION(S): PRJNA302608
REPOSITORIES: GEO
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Project description:Genome-wide DNA methylation profiling was performed of human mesenchymal stem cells (hMSCs) differentiating into adipocytes (day 10). The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to measure DNA methylation of hMSC before differentiation (day 0) and of adipocytes at day 10 of differentiation. Our aims were to 1) measure genome-wide DNA methylation changes during adipocyte differentiation in primary hMSCs and 2) investigate the relationship between DNA methylation and gene expression regulation in a panel of 84 adipocyte-related genes. Bisulphite converted DNA from four independent experiments was hybridised to the Illumina Infinium 450k Human Methylation Beadchip. The first comparison was made between undifferentiated hMSCs and differentiated adipocytes at day 10. As a positive control, differentiating cells were continuously exposed to 5-Aza-2â²-deoxycytidine (5-aza-dC). The second comparison was made between differentiated adipocytes at day 10 and 5-aza-dC exposed adipocytes at day 10.
2016-04-13 | E-GEOD-74609 | biostudies-arrayexpress
Project description:Genome-wide DNA methylation profiling was performed in Dutch men consuming eel from relatively low- or high-polluted areas, resulting in a broad range of serum POP levels. The Illumina Infinium 450K Human DNA methylation Beadchip v1.0HD was used to measure DNA methylation in these men and associate this with serum levels of persistent organic pollutants (POPs). In total 48 POPs were measured, of which 30 POPs had levels above the detection limit in at least 60% of the participants. Furthermore, 11 different clinical parameters were measured as biomarkers for health. The leukocyte count was measured in each sample to adjust DNA methylation values. Furthermore, participants reported possible confounders in a questionnaire.
2017-03-06 | GSE79329 | GEO
Project description:Genome-wide DNA methylation profiling was performed of human mesenchymal stem cells (hMSCs) differentiating into adipocytes (day 10). The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to measure DNA methylation of hMSC before differentiation (day 0) and of adipocytes at day 10 of differentiation. Our aims were to 1) measure genome-wide DNA methylation changes during adipocyte differentiation in primary hMSCs and 2) investigate the relationship between DNA methylation and gene expression regulation in a panel of 84 adipocyte-related genes.
2016-04-13 | GSE74609 | GEO
Project description:hMSCs (Lonza) were differentiated towards adipocytes with three cycles of adipocyte differentiation induction and maintenance. hMSCs were differentiated towards osteocytes with osteogenic differentiation medium for 3 days and for 7 days. ArrayCGH experiments were performed before differentiation induction, after 2 and 3 cycles of adipogenic differentiation induction and after 3 days and 7 days of osteogenic differentiation induction.
2016-10-20 | GSE88947 | GEO
Project description:Exposure to persistent organic pollutants (POPs), such as dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs), has historically been linked to population collapses in wildlife. Despite international regulations, these legacy chemicals are still currently detected in women of reproductive age, and their levels correlate with reduced ovarian reserve, longer time-to-pregnancy, and higher risk of infertility. However, the specific modes of action underlying these associations remain unclear. Here, we examined the effects of five commonly occurring POPs − hexachlorobenzene (HCB), p,p'-dichlorodiphenyldichloroethylene (DDE), 2,3,3′,4,4′,5-hexachlorobiphenyl (PCB156), 2,2′,3,4,4′,5,5′-heptachlorobiphenyl (PCB180), perfluorooctane sulfonate (PFOS) − and their mixture on human ovaries in vitro. We exposed human ovarian cancer cell lines COV434, KGN, and PA1 as well as primary ovarian cells for 24 h, and ovarian tissue containing unilaminar follicles for 6 days. RNA-sequencing of samples exposed to concentrations covering epidemiologically relevant levels revealed significant gene expression changes related to central energy metabolism in the exposed cells, indicating glycolysis, oxidative phosphorylation, fatty acid metabolism, and reactive oxygen species as potential shared targets of POP exposures in ovarian cells. Alpha-enolase (ENO1), lactate dehydrogenase A (LDHA), cytochrome C oxidase subunit 4I1 (COX4I1), ATP synthase F1 subunit alpha (ATP5A), and glutathione peroxidase 4 (GPX4) were validated as targets through qPCR in additional cell culture experiments in KGN. In ovarian tissue cultures, we observed significant effects of exposure on follicle growth and atresia as well as protein expression. All POP exposures, except PCB180, decreased unilaminar follicle proportion and increased follicle atresia. Immunostaining confirmed altered expression of LDHA, ATP5A, and GPX4 in the exposed tissues. Moreover, POP exposures modified ATP production in KGN and tissue culture. In conclusion, our results demonstrate the disruption of cellular energy metabolism as a novel mode of action underlying POP-mediated interference of follicle growth in human ovaries.
2024-05-03 | GSE252776 | GEO
Project description:The exposure to and contamination by Persistent Organic Pollutants (POPs), which include pesticides used worldwide and polyaromatic hydrocarbons, is detrimental to human health and diverse ecosystems. Although most mechanistic studies have focused on single compounds, living organisms are exposed to multiple environmental xenobiotics, simultaneously, throughout their lives. The experimental evidence useful for assessing the effects of exposure to pollutant mixtures is scarce. We investigated the effects of exposure to a combination of two POPs, which employ different xenosensors, on global gene expression in a human hepatocyte cell model, HepaRG. Whole genome microarrays were used to investigate the effects on the HepaRG transcriptome following exposure to the combination of POPs as compared to each compound individually. Differentiated HepaRG cells were treated with either 2,3,7,8 tetrachlorodibenzo-p-dioxin, alpha-endosulfan (an organochlorine pesticide), the mixture or the DMSO vehicle for 30 hours after which RNA was extracted for hybridization on Affymetrix whole human genome microarrays.
2016-07-03 | E-GEOD-46874 | biostudies-arrayexpress
Project description:Complex mixtures of persistent organic pollutants (POPs) are regularly detected in the environment and animal tissues. Often these chemicals are associated with latent effects following early-life exposures, following the developmental origin of health and disease paradigm. We investigated the long-term effects of a human relevant mixture of 29 POPs on adult zebrafish following a developmental exposure, in addition to a single PFOS exposure for comparison, as it was the compound with the highest concentration within the mixture. Zebrafish embryos were exposed from 6 to 96 hours post fertilization to x10 and x70 the level of POP mixture or PFOS found in human blood before being transferred to clean water. We measured growth, swimming performance, and reproductive output at different life stages. In addition, we assessed anxiety behavior of the adults and their offspring, as well as performing a transcriptomic analysis on the adult zebrafish brain, as the POP mixture and PFOS concentrations used are known to affect larval behavior. Exposure to POP mixture and PFOS reduced swimming performance and increased length and weight, compared to controls. No effect of developmental exposure was observed on reproductive output or anxiety behavior. Additionally, RNA-seq did not reveal pathways related to anxiety although pathways related to synapse biology were affected at the x10 PFOS level. Furthermore, pathway analysis of the brain transcriptome of adults exposed as larvae to the low concentration of PFOS revealed enrichment in pathways such as calcium, MAPK, and GABA signaling, all of which are important for learning and memory. Based on our results we can conclude that some effects on the endpoints measured were apparent, but if these effects lead to adversities at population levels remains elusive.
2020-12-03 | GSE162503 | GEO
Project description:Abstract Background In obesity, adipose tissue undergoes a remodeling process characterized by increased adipocyte size (hypertrophia) and number (hyperplasia). The individual ability to tip the balance toward the hyperplastic growth, with recruitment of new fat cells through adipogenesis, seems to be critical for a healthy adipose tissue expansion, as opposed to the development of inflammation and detrimental metabolic consequences. However, the molecular mechanisms underlying this fine-tuned regulation are far from being understood. Methods We analyzed by mass spectrometry-based proteomics visceral white adipose tissue (vWAT) samples collected from C57BL6 mice fed with a HFD for 8 weeks. A subset of these mice, called low responders (LowR HFD), showed a low susceptibility to the onset of adipose tissue inflammation, as opposed to their HFD counterpart. We identified the discriminants between LowR HFD and HFD vWAT samples and explored their function in Adipose Derived human Mesenchymal Stem Cells (AD-hMSCs) differentiated to adipocytes. Results We quantified 6051 proteins. Among the candidates that most differentiate LowR HFD from HFD vWAT, we found proteins involved in adipocyte function, including adiponectin and hormone sensitive lipase, suggesting that adipocyte differentiation is enhanced in LowR HFD, as compared to HFD. The chromatin modifier SET and MYND Domain Containing 3 (SMYD3), whose function in adipose tissue was totally unknown, was another top-scored hit. SMYD3 expression was significantly higher in LowR HFD vWAT, as confirmed by western blot analysis. In vitro, we found that SMYD3 mRNA and protein levels decrease rapidly along the differentiation process of AD-hMSCs. Moreover, SMYD3 knock-down at the beginning of adipocyte differentiation resulted in reduced cell proliferation and, at longer term, reduced lipid accumulation in adipocytes. Conclusions Our study describes for the first time the role of SMYD3 as a regulator of adipocyte proliferation during the early steps of adipogenesis.
2024-01-03 | PXD043165 | Pride
Project description:Cyclopropanes-functionalized hydrocarbons are excellent fuels. however, their synthesis is challenging and harmful for the environment. In this work we produced polycyclopropanated fatty acids in bacteria. These molecules can be easily converted into renewable fuels for high energy applications such as shipping, long-haul transport, aviation, and rocketry. We explored the chemical diversity encoded in the genome of thousands of bacteria to identify and repurpose naturally occurring cyclopropanated molecules. We identified a set of candidate iterative Polyketide Synthases (iPKSs) predicted to produce polycyclopropanated fatty acids (POP-FAs), expressed these PKSs in Streptomyces coelicolor and produced the POP-FAs. We determined the structure of the molecules and increased their production 22-fold. Polycyclopropanated fatty acid methyl esters (POP-FAMEs) were obtained by methyl esterifying the POP-FAs. Finally, we calculated the enthalpy of combustion of several POP fuel candidates to assess their potential as replacement for fossil fuels in energy demanding applications. Our research shows that POP-FAMEs and other polyketide derived POPs have the energetic properties for energy demanding applications for which sustainable alternatives are scarce.
2022-09-19 | PXD031402 | Pride
Project description:The exposure to and contamination by Persistent Organic Pollutants (POPs), which include pesticides used worldwide and polyaromatic hydrocarbons, is detrimental to human health and diverse ecosystems. Although most mechanistic studies have focused on single compounds, living organisms are exposed to multiple environmental xenobiotics, simultaneously, throughout their lives. The experimental evidence useful for assessing the effects of exposure to pollutant mixtures is scarce. We investigated the effects of exposure to a combination of two POPs, which employ different xenosensors, on global gene expression in a human hepatocyte cell model, HepaRG. Whole genome microarrays were used to investigate the effects on the HepaRG transcriptome following exposure to the combination of POPs as compared to each compound individually.
2016-01-01 | GSE46874 | GEO