Freshwater Cyanotoxin Cylindrospermopsin Has Detrimental Stage-specific Effects on Hepatic Differentiation From Human Embryonic Stem Cells
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
30500929
DOI
10.1093/toxsci/kfy293
PII: 5220775
Knihovny.cz E-zdroje
- Klíčová slova
- cyanotoxin, cylindrospermopsin, hepatic differentiation, human embryonic stem cells, liver,
- MeSH
- albuminy metabolismus MeSH
- alkaloidy MeSH
- apoptóza MeSH
- bakteriální toxiny toxicita MeSH
- buněčná diferenciace účinky léků MeSH
- hepatocytární jaderný faktor 4 metabolismus MeSH
- hepatocyty účinky léků MeSH
- játra účinky léků MeSH
- kmenové buňky MeSH
- lidé MeSH
- lidské embryonální kmenové buňky MeSH
- metabolismus lipidů MeSH
- nekróza MeSH
- oxidační stres účinky léků MeSH
- sinice MeSH
- sladká voda MeSH
- toxiny kmene Cyanobacteria MeSH
- uracil analogy a deriváty toxicita MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- albuminy MeSH
- alkaloidy MeSH
- bakteriální toxiny MeSH
- cylindrospermopsin MeSH Prohlížeč
- hepatocytární jaderný faktor 4 MeSH
- HNF4A protein, human MeSH Prohlížeč
- toxiny kmene Cyanobacteria 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
Citace poskytuje Crossref.org
