DNA methylation profiles in human iPSC-derived neurosphere exposed to environmental chemicals
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PROVIDER: PRJNA984667 | ENA |
REPOSITORIES: ENA
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Project description:Various chemicals, including pesticides, heavy metals, and metabolites of tobacco, have been detected in fetal environment. Fetuses are exposed to these chemicals at relatively low concentrations; however, their risk of developing neurological and behavioral disorders increases after birth. We aimed to evaluate the effects of five chemicals (diethylphosphate, cotinine, octachlorodipropyl ether, mercury, and selenium) detected in the serum of pregnant mothers on DNA methylation status during neural development using human neural stem cells.
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Project description:Exposure to environmental chemicals can impair neurodevelopment, and oligodendrocytes may be particularly vulnerable as their development extends from gestation into adulthood. However, few environmental chemicals have been assessed for potential risks to oligodendrocytes. Here, using a high-throughput developmental screen in cultured cells, we identified environmental chemicals in two classes that disrupt oligodendrocyte development through distinct mechanisms. Quaternary compounds, ubiquitous in disinfecting agents and personal care products, were potently and selectively cytotoxic to developing oligodendrocytes, whereas organophosphate flame retardants, commonly found in household items such as furniture and electronics, prematurely arrested oligodendrocyte maturation. Chemicals from each class impaired oligodendrocyte development postnatally in mice and in a human 3D organoid model of prenatal cortical development. Analysis of epidemiological data showed that adverse neurodevelopmental outcomes were associated with childhood exposure to the top organophosphate flame retardant identified by our screen. This work identifies toxicological vulnerabilities for oligodendrocyte development and highlights the need for deeper scrutiny of these compounds’ impacts on human health.
2024-01-25 | GSE244500 | GEO
Project description:Exposure to environmental chemicals can impair neurodevelopment. Oligodendrocytes that wrap around axons to boost neurotransmission may be particularly vulnerable to chemical toxicity as they develop throughout fetal development and into adulthood. However, few environmental chemicals have been assessed for potential risks to oligodendrocyte development. Here, we utilized a high-throughput developmental screen and human cortical brain organoids, which revealed environmental chemicals in two classes that disrupt oligodendrocyte development. Quaternary compounds, ubiquitous in disinfecting agents, hair conditioners, and fabric softeners, were potently and selectively cytotoxic to developing oligodendrocytes through activation of the integrated stress response. Organophosphate flame retardants, commonly found in household items such as furniture and electronics, were non-cytotoxic but prematurely arrested oligodendrocyte maturation. Chemicals from each of the two classes impaired human oligodendrocyte development in a 3D organoid model of prenatal cortical development. In analysis of epidemiological data from the CDC’s National Health and Nutrition Examination Survey, adverse neurodevelopmental outcomes were associated with childhood exposure to the top organophosphate flame retardant identified in our oligodendrocyte toxicity platform. Collectively, our work identifies toxicological vulnerabilities specific to oligodendrocyte development and highlights common household chemicals with high exposure risk to children that warrant deeper scrutiny for their impact on human health.
2023-05-31 | GSE212190 | GEO
Project description:We performed an untargeted metabolomic analysis on surficial human skin samples collected with moistened cotton swabs (water: ethanol, 50:50) using LC-HR-MS/MS. Data-dependent Acquisition was employed under positive ionization mode. Two cohorts were included, subjects exposed and non-exposed to petroleum-based chemicals.
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Project description:Recent reports have emphasized the pitfalls of iPSC technology including the potential for immunogenicity of transplanted cells. It is serious safety-related concern for iPSC-based cell therapy. However, preclinical data supporting the safety and efficacy of iPSCs are also accumulating. To address the concern of immunogenicity of ESCs/iPSCs or ESCs/iPSCs-derived neurospheres, global gene expression profiles were compared between undifferentiated mouse ESCs (EB3 line), mouse iPSCs (38C2 line), and ESC/iPSC-derived neurosphere and mouse primary culture of neurosphere obtained from fetal mouse ganglionic eminence. Mouse adult sklin fibroblast was used as a control. We used affymetrix microarrays to compare the global gene expression of neurospheres prepared several origins. Keywords: Expression profiling by array
2012-03-01 | GSE31725 | GEO
Project description:Pervasive environmental chemicals impair oligodendrocyte development
| PRJNA1023278 | ENA