Single cell RNA sequencing detects persistent cell type- and methylmercury exposure paradigm-specific effects in a human cortical neurodevelopmental model
| Autor: | Jyothi Thimmapuram, Shaojun Xie, Aaron B. Bowman, Hyunjin Kim, Anke M Tukker, M. Diana Neely, Lisa M. Prince, Michael Aschner |
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| Rok vydání: | 2021 |
| Předmět: |
Cell type
Induced Pluripotent Stem Cells Cell Apoptosis Biology Toxicology Models Biological Article 03 medical and health sciences 0404 agricultural biotechnology Gene expression medicine Humans Induced pluripotent stem cell 030304 developmental biology Cerebral Cortex Neurons 0303 health sciences Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis RNA Cell Cycle Reproducibility of Results Cell Differentiation 04 agricultural and veterinary sciences General Medicine Human brain Methylmercury Compounds Cell cycle Glutathione 040401 food science Cortex (botany) Cell biology medicine.anatomical_structure Gene Expression Regulation Neuron Single-Cell Analysis Food Science |
| Zdroj: | Food Chem Toxicol |
| ISSN: | 0278-6915 |
| DOI: | 10.1016/j.fct.2021.112288 |
| Popis: | The developing human brain is uniquely vulnerable to methylmercury (MeHg) resulting in lasting effects especially in developing cortical structures. Here we assess by single-cell RNA sequencing (scRNAseq) persistent effects of developmental MeHg exposure in a differentiating cortical human-induced pluripotent stem cell (hiPSC) model which we exposed to in vivo relevant and non-cytotoxic MeHg (0.1 and 1.0 μM) concentrations. The cultures were exposed continuously for 6 days either once only during days 4–10, a stage representative of neural epithelial- and radial glia cells, or twice on days 4–10 and days 14–20, a somewhat later stage which includes intermediate precursors and early postmitotic neurons. After the completion of MeHg exposure the cultures were differentiated further until day 38 and then assessed for persistent MeHg-induced effects by scRNAseq. We report subtle, but significant changes in the population size of different cortical cell types/stages and cell cycle. We also observe MeHg-dependent differential gene expression and altered biological processes as determined by Gene Ontology analysis. Our data demonstrate that MeHg results in changes in gene expression in human developing cortical neurons that manifest well after cessation of exposure and that these changes are cell type-, developmental stage-, and exposure paradigm-specific. |
| Databáze: | OpenAIRE |
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