ArticleToxicological sciences : an official journal of the Society of Toxicology2020
Single-Cell Analysis of the Gene Expression Effects of Developmental Lead (Pb) Exposure on the Mouse Hippocampus.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- Cell composition, transcriptomic, and functional pathway changes in the hippocampus in Alzheimer's disease and overlap with lead (Pb) exposure signatures.medRxiv : the preprint server for health sciences · 2026Article
- Environmentally relevant lead exposure impacts gene expression in SH-SY5Y cells throughout neuronal differentiation.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Perinatal Lead (Pb) Exposure Increases Mouse Embryonic Weight and Alters Neuronal Gene Expression.bioRxiv : the preprint server for biology · 2025Article
- Rapid Dissection and Dissociation of the Mouse Olfactory Epithelium for Single-Nucleus Suspensions.Journal of visualized experiments : JoVE · 2025Article
- Sex and tissue-specificity of piRNA regulation in adult mice following perinatal lead (Pb) exposure.Epigenetics · 2024Article
- Demyelination and impaired oligodendrogenesis in the corpus callosum following lead exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Lead Decreases Bone Morphogenetic Protein-7 (BMP-7) Expression and Increases Renal Cell Carcinoma Growth in a Sex-Divergent Manner.International journal of molecular sciences · 2024Article
- Single-cell investigation of lead toxicity from neurodevelopment to neurodegeneration: Current review and future opportunities.Current opinion in toxicology · 2024Article
- Response to "Comment on 'Neurotoxicity and Outcomes from Developmental Lead Exposure: Persistent or Permanent?'".Environmental health perspectives · 2024Article
- Application of Single Cell Gene Expression Technologies to Neurotoxicology.Current opinion in toxicology · 2024Article
- Placental single cell transcriptomics: Opportunities for endocrine disrupting chemical toxicology.Molecular and cellular endocrinology · 2023Article
- Perinatal Lead Exposure Promotes Sex-Specific Epigenetic Programming of Disease-Relevant Pathways in Mouse Heart.Toxics · 2023Article
- Gene-environment interactions in Alzheimer disease: the emerging role of epigenetics.Nature reviews. Neurology · 2022Review
- Article
- Toxicoepigenetics and Environmental Health: Challenges and Opportunities.Chemical research in toxicology · 2022Review
- Sodium para-aminosalicylic acid ameliorates lead-induced hippocampal neuronal apoptosis by suppressing the activation of the IPEcotoxicology and environmental safety · 2022Article
- Single-Cell Sequencing Analysis of the db/db Mouse Hippocampus Reveals Cell-Type-Specific Insights Into the Pathobiology of Diabetes-Associated Cognitive Dysfunction.Frontiers in endocrinology · 2022Article
- Prenatal Lead (Pb) Exposure and Peripheral Blood DNA Methylation (5mC) and Hydroxymethylation (5hmC) in Mexican Adolescents from the ELEMENT Birth Cohort.Environmental health perspectives · 2021Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Lead (Pb) exposure is ubiquitous with permanent neurodevelopmental effects. The hippocampus brain region is involved in learning and memory with heterogeneous cellular composition. The hippocampus cell type-specific responses to Pb are unknown. The objective of this study is to examine perinatal Pb treatment effects on adult hippocampus gene expression, at the level of individual cells. In mice perinatally exposed to control water or a human physiologically relevant level (32 ppm in maternal drinking water) of Pb, 2 weeks prior to mating through weaning, we tested for hippocampus gene expression and cellular differences at 5 months of age. We sequenced RNA from 5258 hippocampal cells to (1) test for treatment gene expression differences averaged across all cells, (2) compare cell cluster composition by treatment, and (3) test for treatment gene expression and pathway differences within cell clusters. Gene expression patterns revealed 12 hippocampus cell clusters, mapping to major expected cell types (eg, microglia, astrocytes, neurons, and oligodendrocytes). Perinatal Pb treatment was associated with 12.4% more oligodendrocytes (p = 4.4 × 10-21) in adult mice. Across all cells, Pb treatment was associated with expression of cell cluster marker genes. Within cell clusters, Pb treatment (q < 0.05) caused differential gene expression in endothelial, microglial, pericyte, and astrocyte cells. Pb treatment upregulated protein folding pathways in microglia (p = 3.4 × 10-9) and stress response in oligodendrocytes (p = 3.2 × 10-5). Bulk tissue analysis may be influenced by changes in cell type composition, obscuring effects within vulnerable cell types. This study serves as a biological reference for future single-cell toxicant studies, to ultimately characterize molecular effects on cognition and behavior.
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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.