Single cell RNA sequencing detects persistent cell type- and methylmercury exposure paradigm-specific effects in a human cortical neurodevelopmental model.
Food Chem Toxicol
; 154: 112288, 2021 Aug.
Article
em En
| MEDLINE
| ID: mdl-34089799
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Córtex Cerebral
/
Análise de Sequência de RNA
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Análise de Célula Única
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Compostos de Metilmercúrio
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Food Chem Toxicol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos