Expression data from Human bone mesenchymal stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE115836 | GEO | 2019/12/31
REPOSITORIES: GEO
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2020-07-07 | GSE146489 | GEO
Project description:Humans can be exposed to per- and polyfluoroalkyl substances (PFASs) via many exposure routes, including diet, which may lead to several adverse health effects. So far, little is known about PFAS transport across the human intestinal barrier. In the current study, we aimed to assess the transport of 5 PFASs (PFOS, PFOA, PFNA, PFHxS and HFPO-DA) in a human induced pluripotent stem cell (hiPSC)-derived intestinal epithelial cell (IEC) model. This model was extensively characterized and compared with the widely applied human colonic adenocarcinoma cell line Caco-2 and a human primary IEC-based model, described to most closely resemble in vivo tissue. The hiPSC-derived IEC layers demonstrated polarized monolayers with tight junctions and a mucus layer. The monolayers consisted of enterocytes, stem cells, goblet cells, enteroendocrine cells, and Paneth cells that are also present in native tissue. Transcriptomics analysis revealed distinct differences in gene expression profiles where the hiPSC-derived IECs showed highest expression of intestinal tissue-specific genes relative to the primary IEC-based model, whereas the Caco-2 cells clustered closer to the primary IEC-based model than the hiPSC-derived IECs. The order of PFAS transport was largely similar between the models and the apparent permeability (Papp) values of PFAS in apical to basolateral direction in the hiPSC-derived IEC model were in the following order: PFHxS>PFOA>HFPO-DA>PFNA>PFOS. In conclusion, the hiPSC-derived IEC model highly resembles human intestinal physiology and is therefore a promising novel in vitro model to study transport of chemicals across the intestinal barrier for risk assessment of chemicals.
2024-06-05 | GSE268603 | GEO
Project description:Multiple per- and polyfluoroalkyl substances (PFAS) have been associated with adverse liver outcomes in adult humans and toxicological models, but effects on the developing liver or biologic pathways involved are not known. We performed whole-transcriptome gene expression analysis to investigate the molecular mechanisms of liver toxicity in the dam and female fetuses after exposure to two different PFAS, perfluorooctanoic acid (PFOA) and its replacement, hexafluoropropylene oxide-dimer acid (HFPO-DA, commonly referred to as GenX).
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Project description:Perfluoroalkyl substances (PFAS) are a group of synthetic chemicals that are resistant to biodegradation and are environmentally persistent. PFAS are found in many consumer products including non-stick cookware, food packaging materials, upholstery, and personal care products. Accordingly, PFAS are a major source of water and soil contamination. Although use of many PFAS have been phased out, they continue to be detected in human and animal fluids, including human follicular fluid. This study investigated the effects of an environmentally relevant PFAS mixture [perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS)] on the transcriptome and function of human granulosa cells (hGCs). PFOA, PFOS, and PFHxS were detected in 100% of follicle fluid samples. Increased cell proliferation was observed in hGCs treated with the PFAS mixture with no impacts on cellular apoptosis. The PFAS mixture also altered steroid hormone synthesis, increasing both FSH-stimulated and basal progesterone secretion and concomitant upregulation of STAR protein. RNA sequencing revealed inherent differences in transcriptomic profiles in hGCs after PFAS exposure. This study demonstrates functional and transcriptomic changes in hGCs after exposure to a PFAS mixture, improving our knowledge about the impacts of PFAS exposures and female reproductive health. These findings suggest that PFAS compounds have the potential to disrupt normal granulosa cell function with possible long-term consequences on overall reproductive health.
2024-07-03 | GSE246371 | GEO
Project description:PFAS are widely used in commercial products, and so humans have consistent exposure to them via oil- and water-resistant consumer products, fire- fighting foam, and industrial surfactants 1,2. The four PFASs commonly detected in blood, perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) 3,4, are present in drinking water supplies both in northern New England as well as in 27 states nationally 5-8. Animal models shows that PFASs have can have effects on both the endocrine system and on adiposity 9-12. Epidemiological evidence shows that the presence of PFASs in maternal serum is associated with changes in maternal serum lipid and cholesterol composition 13,14. Similarly, serum levels of PFAS in adolescents have been associated with increases in serum cholesterol 15. These findings raise interesting questions about the association of PFAS and lipids in human milk. Research has shown the PFASs are present in human milk 16-18, and human milk is composed primarily of lipids 19. However, the relation between PFAS in milk and milk composition is unclear. The chemical and compositional profiles of breast milk are important because of the potential effects on the developing infant. The developmental origins of health and disease hypothesis suggests that early life exposures, such as toxins and nutrients via breast milk, have lasting effects on health, particularly obesity outcomes 20. In fact, some studies have shown associations between PFAS in maternal serum and infant birth weight and later childhood BMI 14,21. Our study will help to better illuminate the potential effects of maternal exposure to PFASs on infant exposure, both through direct transmission into breast milk and indirectly via influence on the lipid profiles of milk. To investigate how early life exposure to perfluoroalkyl substances (PFAS) may affect childhood health outcomes as mediated through breast milk, we propose the following specific aims: 1. Characterize the levels of PFAS in breast milk samples (n=495) in the NHBCS; 2. Characterize the lipid profiles of breast milk samples (n=495) in the NHBCS; 3. Test the relation between PFAS concentration and breast milk lipid profiles; and 4. Test the association between PFAS concentrations in maternal plasma collected during pregnancy with paired breast milk samples (n=100).
2021-02-10 | ST001692 | MetabolomicsWorkbench
Project description:Gene expression data from short-term in vivo studies shows efficacy in quantifying concentration-dependent effects that inform toxicity outcomes, particularly for chemicals with limited toxicity data such as Per- and Polyfluoroalkyl Substances (PFAS). Automated behavioral assessments, at non-teratogenic concentrations reveal perfluorohexane-1-sulfonate (PFHxS) exposure causes hyperactivity in larval zebrafish (6 days post fertilization (dpf)) during the light phase of the light:dark assay compared to 0.4% dimethylsulfoxide (DMSO) vehicle control. To identify key events that drive this abnormal behavior, zebrafish embryos were exposed to 7.87-25.1 μM PFHxS or 0.4% DMSO, and RNA was isolated from pooled head tissue collected at 4 and 5 dpf, before the onset of hyperactivity, for RNA-sequencing (NextSeq 500). Differentially expressed genes (DEGs) were identified using Gene Specific Analysis (Partek Flow, St. Louis, MO) and mapped to human orthologs for pathway analyses to inform modes of action.
2023-05-08 | GSE190009 | GEO
Project description:Background: Previously, we reported that perfluorooctanoic acid (PFOA) promotes liver cancer in manner similar to that of 17β-estradiol (E2) in rainbow trout. Also, other perfluoroalkyl acids (PFAAs) are weakly estrogenic in trout and bind the trout liver estrogen receptor (ER). Objectives: The primary objective of this study was to determine whether multiple PFAAs enhance hepatic tumorigenesis in trout, an animal model that represents human insensitivity to peroxisome proliferators. Methods: A two-stage chemical carcinogenesis model was employed in trout to evaluate PFOA, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorooctane sulfonate (PFOS) and 8:2 fluorotelomer alcohol (8:2FtOH) as complete carcinogens or promoters of aflatoxin B1 (AFB1)- and/or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced liver cancer. A custom trout DNA microarray was used to assess hepatic transcriptional response to these dietary treatments in comparison to E2 and the classic peroxisome proliferator clofibrate (CLOF). Results: Incidence, multiplicity and size of liver tumors in trout fed diets containing E2, PFOA, PFNA and PFDA were significantly higher compared to AFB1-initiated animals fed control diet, whereas PFOS caused a minor increase in liver tumor incidence. E2 and PFOA also enhanced MNNG-initiated hepatocarcinogenesis. Pearson correlation analyses, unsupervised hierarchical clustering and principal components analyses showed that the hepatic gene expression profiles for E2 and PFOA, PFNA, PFDA and PFOS were overall highly similar, though distinct patterns of gene expression were evident for each treatment, particularly for PFNA. Conclusions: Overall, these data suggest that multiple PFAAs can promote liver cancer and that the mechanism of promotion may be similar to that for E2. A total of 40 samples were analyzed using a a dye-swap, reference sample hybridization protocol. Rainbow trout were exposed to the following experimental treatments via the diet for two weeks (number in parenthesis is assigned group #): (1) Control; (2) 5 mg/kg diet estradiol (E2); (3) 2000 mg/kg diet perfluorooctanoic acid (PFOA); (4) 2000 mg/kg diet perfluorononanoic acid (PFNA); (5) 2000 mg/kg diet perfluorodecanoic acid (PFDA); (6) 200 mg/kg diet perfluorooctane sulfonate; (7) 2000 mg/kg 8:2 fluorotelomer alcohol (FTOH); and (8) 2000 mg/kg diet clofibrate. A total of 40 total hepatic mRNA samples were analyzed using a dye-swap, reference sample hybridization protocol. A reference RNA pool was made by combining equal amounts of RNA from all control RNA samples, with one exception. A separate time-matched reference pool was utilized for group 6 samples (PFOS treatment). Five hybridizations were performed for each treatment group in the following pattern: Replicate A Cy5/Reference Cy3; Replicate A Cy3/Reference Cy 5; Replicate B Cy5/Reference Cy3; Replicate B Cy3/Reference Cy5; Replicate C Cy5/Reference Cy3. Thus, the experiment consisted of three biological replicates, for two of which were replicated technically.
2011-08-01 | E-GEOD-31085 | biostudies-arrayexpress
Project description:The objective of our study is to investigate the effect of PFOA and GenX on the gene expression levels in Monodelphis domestica whole blood cultures by RNA-seq and identify the major susceptible genes. We identified 578 differentially expressed genes (DEGs) in the PFOA treatment group and 148 DEGs in the GenX treatment group. 10 genes were selected for qRT-PCR validation and were confirmed to be DEGs. Pathway enrichment analysis revealed that several developmental processes were altered after PFOA exposure and showed an up-regulated pattern. And down-regulated DEGs after PFOA exposure were enriched for metabolic process and immune system process. GenX exposure is associated with up-regulated fatty acid transport pathways and inflammatory process. Our study is the first one to investigate the effects of PFASs on marsupial animals, providing supportive evidence of the similar transcriptomic alterations caused by PFOA and a fluorinated alternative GenX, which can work as a complement of the previous studies of PFASs effects on rodent or human.
2022-10-15 | GSE208237 | GEO
Project description:PFAS are persistent man-made chemicals considered to be emerging pollutants, with PFOA, PFOS, and PFHxS having associations with liver toxicity and steatosis. PFOA, PFOS, and PFHxS can undergo placental/lactational transfer, however, little is known about the impact of PFAS mixtures during the developmental window, nor maternal diet on PFAS adverse effects. It was hypothesized that gestational/lactational PFAS exposure would alter the pup liver proteome. The work herein evaluated the liver proteome in offspring, identifying potential biochemical/signaling pathways altered via maternal PFAS exposure. Timed-pregnant CD-1 dams were fed a standard chow or 60% kcal high-fat diet. From GD1 until PND20, dams were orally gavaged daily with either 0.5% Tween 20, individual PFOA, PFOS, PFHxS at 1 mg/kg, or a mixture (1 mg/kg each, totaling 3 mg/kg). Livers were collected from PND21 offspring and SWATH-MS pro-teomics was performed. IPA analysis revealed disease and biological function pathways involved in liver damage, xenobiotics, and lipid regulation were modulated by PFAS exposure in the PND21 liver: lipid transport, storage, oxidation, and synthesis, xenobiotic metabolism and transport, liver damage and inflammation, and fatty acid metabolism, oxidation and transport. This indicates the pup liver proteome is altered via maternal exposure and predisposes the pup to metabolic dysfunctions.
2024-05-09 | PXD052106 | Pride
Project description:The renal clearance of perfluorooctanoic acid (PFOA) increased in Abcb4 null mice compared with wild type mice, especially in male Abcb4 null mice. We evaluated the expression changes of transporters in kidney of male Abcb4 null mice by using microarray to reveal the candidate transporters of PFOA.
2011-06-21 | GSE30084 | GEO