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@article{1603936,
author = {Váňová, Tereza and Raška, Jan and Babica, Pavel and Sovadinová, Iva and Bosáková, Michaela and Dvořák, Petr and Bláha, Luděk and Rotrekl, Vladimír},
article_location = {OXFORD},
article_number = {1},
doi = {http://dx.doi.org/10.1093/toxsci/kfy293},
keywords = {cylindrospermopsin; hepatic differentiation; human embryonic stem cells; liver; cyanotoxin},
language = {eng},
issn = {1096-6080},
journal = {Toxicological sciences},
title = {Freshwater Cyanotoxin Cylindrospermopsin Has Detrimental Stage-specific Effects on Hepatic Differentiation From Human Embryonic Stem Cells},
url = {http://dx.doi.org/10.1093/toxsci/kfy293},
volume = {168},
year = {2019}
}
TY - JOUR
ID - 1603936
AU - Váňová, Tereza - Raška, Jan - Babica, Pavel - Sovadinová, Iva - Bosáková, Michaela - Dvořák, Petr - Bláha, Luděk - Rotrekl, Vladimír
PY - 2019
TI - Freshwater Cyanotoxin Cylindrospermopsin Has Detrimental Stage-specific Effects on Hepatic Differentiation From Human Embryonic Stem Cells
JF - Toxicological sciences
VL - 168
IS - 1
SP - 241-251
EP - 241-251
PB - Academic Press
SN - 10966080
KW - cylindrospermopsin
KW - hepatic differentiation
KW - human embryonic stem cells
KW - liver
KW - cyanotoxin
UR - http://dx.doi.org/10.1093/toxsci/kfy293
L2 - http://dx.doi.org/10.1093/toxsci/kfy293
N2 - 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 HNF4+ 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.
ER -
VÁŇOVÁ, Tereza, Jan RAŠKA, Pavel BABICA, Iva SOVADINOVÁ, Michaela BOSÁKOVÁ, Petr DVOŘÁK, Luděk BLÁHA and Vladimír ROTREKL. Freshwater Cyanotoxin Cylindrospermopsin Has Detrimental Stage-specific Effects on Hepatic Differentiation From Human Embryonic Stem Cells. \textit{Toxicological sciences}. OXFORD: Academic Press, 2019, vol.~168, No~1, p.~241-251. ISSN~1096-6080. Available from: https://dx.doi.org/10.1093/toxsci/kfy293.
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