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Differentiation and Characterization of Neural Progenitors and Neurons from Mouse Embryonic Stem Cells
Published on: May 15, 2020
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Long-term arsenic exposure impairs differentiation in mouse embryonal stem cells.
Benjamin D McMichael1,2, M Chiara Perego1, Caitlin L Darling1
1Environmental Toxicology Graduate Program, Clemson University, Clemson, South Carolina, USA.
Journal of Applied Toxicology : JAT
|October 30, 2020
Summary
Chronic arsenic exposure may hinder neuronal development. This study found that low-level arsenic exposure in mouse stem cells increased pluripotency markers and reduced differentiation markers, suggesting a delay in neuronal differentiation.
Area of Science:
- Developmental neurobiology
- Toxicology
- Stem cell biology
Background:
- Arsenic is a widespread environmental contaminant.
- Developmental exposure to arsenic can disrupt neuronal progenitor cell development and function.
- In vitro studies show acute arsenic exposure impairs stem and progenitor cell differentiation.
Purpose of the Study:
- To investigate the temporal effects of chronic, low-level arsenic exposure on P19 mouse embryonal stem cells.
- To examine changes in pluripotency and neuronal differentiation markers over 32 weeks of arsenic exposure.
Main Methods:
- P19 mouse embryonal stem cells were continuously exposed to 0.1-μM (7.5 ppb) arsenic for 32 weeks.
- Cell lineage arrays analyzed mRNA expression changes at 8 and 32 weeks.
- Quantitative analysis of key pluripotency (Sox2, Oct4) and differentiation (Gdf3, N-cadherin, Zeb1) markers at mRNA and protein levels.
Main Results:
- Arsenic exposure increased mRNA and protein levels of pluripotency markers Sox2 and Oct4 starting at weeks 12 and 16, respectively.
- N-cadherin and Zeb1, associated with epithelial-mesenchymal transitions and Sox2 regulation, were upregulated by arsenic exposure.
- Expression of differentiation marker Gdf3 and its downstream target phospho-Smad2/3 was significantly reduced.
Conclusions:
- Chronic, low-level arsenic exposure may impede neuronal differentiation by maintaining stem cell pluripotency.
- Arsenic's disruption of developmental pathways warrants further investigation into its long-term neurological effects.
