ArticleThe Science of the total environment2019
Dioxin and AHR impairs mesoderm gene expression and cardiac differentiation in human embryonic stem cells.
Article in The Science of the total environment, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 40 citations in OpenAlex.
- Cathepsin K inhibition promotes efficient differentiation of human embryonic stem cells to mature cardiomyocytes by mediating glucolipid metabolism and cellular energy homeostasis.Stem cell research & therapy · 2025Article
- Fine particulate matter‑induced cardiac developmental toxicity (Review).Experimental and therapeutic medicine · 2025Review
- Advancing Environmental ToxicologyEnvironment & health (Washington, D.C.) · 2024Review
- Engineered platforms for mimicking cardiac development and drug screening.Cellular and molecular life sciences : CMLS · 2024Review
- Investigating the applicability domain of the hiPSC-based PluriLum assay: an embryotoxicity assessment of chemicals and drugs.Archives of toxicology · 2024Article
- Protective Potential of a Botanical-Based Supplement Ingredient against the Impact of Environmental Pollution on Cutaneous and Cardiopulmonary Systems: Preclinical Study.Current issues in molecular biology · 2024Article
- Review
- Developmental Toxicity Studies: The Path towards Humanized 3D Stem Cell-Based Models.International journal of molecular sciences · 2023Review
- A review of food contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin and its toxicity associated with metabolic disorders.Current research in food science · 2023Review
- Human-Based New Approach Methodologies in Developmental Toxicity Testing: A Step Ahead from the State of the Art with a Feto-Placental Organ-on-Chip Platform.International journal of environmental research and public health · 2022Review
- Embryotoxic effects of tribromophenol on early post-implantation development of mouse embryos in vitro.Environmental science and pollution research international · 2022Article
- Inhibition of RNF182 mediated by Bap promotes non-small cell lung cancer progression.Frontiers in oncology · 2022Article
- Converging Roles of the Aryl Hydrocarbon Receptor in Early Embryonic Development, Maintenance of Stemness, and Tissue Repair.Toxicological sciences : an official journal of the Society of Toxicology · 2021Review
- Human Acellular Amniotic Matrix with Previously Seeded Umbilical Cord Mesenchymal Stem Cells Restores Endometrial Function in a Rat Model of Injury.Mediators of inflammation · 2021Article
- Impact of AHR Ligand TCDD on Human Embryonic Stem Cells and Early Differentiation.International journal of molecular sciences · 2020Article
- Meta-Analysis of Transcriptome Data Detected New Potential Players in Response to Dioxin Exposure in Humans.International journal of molecular sciences · 2020Article
- Potential role of polycyclic aromatic hydrocarbons as mediators of cardiovascular effects from combustion particles.Environmental health : a global access science source · 2019Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Dioxin and dioxin-related polychlorinated biphenyls are potent toxicants with association with developmental heart defects and congenital heart diseases. However, the underlying mechanism of their developmental toxicity is not fully understood. Further, different animals show distinct susceptibility and phenotypes after exposure, suggesting possible species-specific effects. Using a human embryonic stem cell (ESC) cardiomyocyte differentiation model, we examined the impact, susceptible window, and dosage of 2,3,7,8‑tetrachlorodibenzo‑p‑dioxin (TCDD) on human cardiac development. We showed that treatment of human ESCs with TCDD at the ESC stage inhibits cardiomyocyte differentiation, and the effect is largely mediated by the aryl hydrocarbon receptor (AHR). We further identified genes that are differentially expressed after TCDD treatment by RNA-sequencing, and genomic regions that are occupied by AHR by chromatin immunoprecipitation and high-throughput sequencing. Our results support the model that TCDD impairs human ESC cardiac differentiation by promoting AHR binding and repression of key mesoderm genes. More importantly, our study demonstrates the toxicity of dioxin in human embryonic development and uncovered a novel mechanism by which dioxin and AHR regulates lineage commitment. It also illustrates the power of ESC-based models in the systematic study of developmental toxicology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.