ArticleToxicological sciences : an official journal of the Society of Toxicology2014
Lead exposure disrupts global DNA methylation in human embryonic stem cells and alters their neuronal differentiation.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 128 citations in OpenAlex.
- Systemic review of genetic and epigenetic factors underlying differential toxicity to environmental lead (Pb) exposure.Environmental science and pollution research international · 2022Pooled it
- A genomics-based framework for identifying biomarkers of human neurodevelopmental toxicity.Reproductive toxicology (Elmsford, N.Y.) · 2016Pooled it
- Transcriptomic effects of lead on the differentiation of human embryonic stem cells into ectoderm: implication for adverse pregnancy outcomes and neurodevelopmental disorders.Archives of toxicology · 2026Article
- Embryonic lead (Pb) contact impairs lipid, oxidative, and behavioral markers in zebrafish across multiple generations.Environmental research · 2026Article
- Perinatal lead (Pb) exposure and alterations to amyloid beta and metabolic profiles in the brain.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Maternal environmental exposure and early-life health risks: The modulating role of nutritional status-A scoping review.iScience · 2026Review
- Gene-specific DNA methylation responses to PbEnvironmental epigenetics · 2026Article
- Environmental Xenobiotics and Epigenetic Modifications: Implications for Human Health and Disease.Journal of xenobiotics · 2025Review
- Pea Peptides and Heavy Metal Neurotoxicity: Exploring Mechanisms and Mitigation Strategies in PC12 Cells.Plant foods for human nutrition (Dordrecht, Netherlands) · 2025Article
- Combined effects of global DNA methylation, blood lead and total urinary arsenic levels on developmental delay in preschool children.Environmental health : a global access science source · 2025Article
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- Review
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- Combined Exposure to Folate and Lead during Pregnancy and Autistic-Like Behaviors among Canadian Children from the MIREC Pregnancy and Birth Cohort.Environmental health perspectives · 2024Article
- Single-cell investigation of lead toxicity from neurodevelopment to neurodegeneration: Current review and future opportunities.Current opinion in toxicology · 2024Article
- Identification of novel NRF2-dependent genes as regulators of lead and arsenic toxicity in neural progenitor cells.Journal of hazardous materials · 2024Article
- Pathological epigenetic events and reversibility review: the intersection between hallmarks of aging and developmental origin of health and disease.Epigenomics · 2023Review
- Joint Action Toxicity of Arsenic (As) and Lead (Pb) Mixtures in Developing Zebrafish.Biomolecules · 2022Article
- Prenatal lead (Pb) exposure is associated with differential placental DNA methylation and hydroxymethylation in a human population.Epigenetics · 2022Article
- Evolutionary Implications of Environmental Toxicant Exposure.Biomedicines · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Exposure to lead (Pb) during childhood can result in learning disabilities and behavioral problems. Although described in animal models, whether Pb exposure also alters neuronal differentiation in the developing brains of exposed children is unknown. Here, we investigated the effects of physiologically relevant concentrations of Pb (from 0.4 to 1.9μM) on the capacity of human embryonic stem cells (hESCs) to progress to a neuronal fate. We found that neither acute nor chronic exposure to Pb prevented hESCs from generating neural progenitor cells (NPCs). NPCs derived from hESCs chronically exposed to 1.9μM Pb throughout the neural differentiation process generated 2.5 times more TUJ1-positive neurons than those derived from control hESCs. Pb exposure of hESCs during the stage of neural rosette formation resulted in a significant decrease in the expression levels of the neural marker genes PAX6 and MSI1. Furthermore, the resulting NPCs differentiated into neurons with shorter neurites and less branching than control neurons, as assessed by Sholl analysis. DNA methylation studies of control, acutely treated hESCs and NPCs derived from chronically exposed hESCs using the Illumina HumanMethylation450 BeadChip demonstrated that Pb exposure induced changes in the methylation status of genes involved in neurogenetic signaling pathways. In summary, our study shows that exposure to Pb subtly alters the neuronal differentiation of exposed hESCs and that these changes could be partly mediated by modifications in the DNA methylation status of genes crucial to brain development.
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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.