Freshwater Cyanotoxin Cylindrospermopsin Has Detrimental Stage-specific Effects on Hepatic Differentiation From Human Embryonic Stem Cells
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
30500929
DOI
10.1093/toxsci/kfy293
PII: 5220775
Knihovny.cz E-resources
- Keywords
- cyanotoxin, cylindrospermopsin, hepatic differentiation, human embryonic stem cells, liver,
- MeSH
- Albumins metabolism MeSH
- Alkaloids MeSH
- Apoptosis MeSH
- Bacterial Toxins toxicity MeSH
- Cell Differentiation drug effects MeSH
- Hepatocyte Nuclear Factor 4 metabolism MeSH
- Hepatocytes drug effects MeSH
- Liver drug effects MeSH
- Stem Cells MeSH
- Humans MeSH
- Human Embryonic Stem Cells MeSH
- Lipid Metabolism MeSH
- Necrosis MeSH
- Oxidative Stress drug effects MeSH
- Cyanobacteria MeSH
- Fresh Water MeSH
- Cyanobacteria Toxins MeSH
- Uracil analogs & derivatives toxicity MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Albumins MeSH
- Alkaloids MeSH
- Bacterial Toxins MeSH
- cylindrospermopsin MeSH Browser
- Hepatocyte Nuclear Factor 4 MeSH
- HNF4A protein, human MeSH Browser
- Cyanobacteria Toxins MeSH
- Uracil MeSH
Cylindrospermopsin (CYN) has been recognized as a potent waterborne hepatotoxin with an increasing environmental occurrence. However, CYN effects on the specific populations of hepatic cells involved in liver tissue development, renewal, and regeneration, have not been characterized yet. We used human embryonic stem cells to analyze the hepatic differentiation stage-specific effect of CYN. Our results strongly suggest that CYN might contribute to the development of chronic adverse outcomes by disrupting liver tissue homeostasis in terms of (1) cellular stress and damage induced in the mature differentiated hepatocytes, which was associated with a necrotic cell death and thus possibly also inflammatory responses; (2) selective elimination of HNF4α+ cells from populations of progenitor cells and immature hepatocytes during hepatic differentiation, which could possibly lead to an impaired liver renewal and regeneration; (3) impaired hepatic functions of immature hepatocytes, such as decreased albumin secretion or increased lipid accumulation, which could contribute to the development of liver steatosis; and (4) survival of the immature and AFP-expressing cells with the limited ability to further differentiate, which could represent a tumor-promoting condition.
Department of Biology Faculty of Medicine
International Clinical Research Center St Anne's University Hospital 62500 Brno Czech Republic
RECETOX Faculty of Science Masaryk University 62500 Brno Czech Republic
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