四溴双酚A
转录组
生物
细胞命运测定
细胞分化
细胞生物学
胚胎干细胞
Wnt信号通路
毒性
细胞生长
发育毒性
信号转导
干细胞
内科学
基因
化学
转录因子
基因表达
胎儿
遗传学
怀孕
医学
有机化学
阻燃剂
作者
Renjun Yang,Shu-Yu Liu,Xiaoxing Liang,Nuoya Yin,Linshu Jiang,Yang Zhang,Francesco Faiola
标识
DOI:10.1016/j.jhazmat.2020.123341
摘要
Halogenated flame retardants (HFRs), including Tetrabromobisphenol A (TBBPA), Tetrabromobisphenol S (TBBPS), and Tetrachlorobisphenol A (TCBPA), are widely applied in the manufacturing industry to improve fire safety and can be detected in pregnant women’s serum at nanomolar levels. Thus, it is necessary to pay attention to the three HFR potential development toxicity, which has not been conclusively addressed yet. The liver is the main organ that detoxifies our body; TBBPA exposure may lead to increased liver weight in rodents. Therefore, in this study, we assessed the developmental hepatic toxicity of the three HFRs with a human embryonic stem cell hepatic differentiation-based system and transcriptomics analyses. We mostly evaluated lineage fate alterations and demonstrated the three HFRs may have common disruptive effects on hepatic differentiation, with TCBPA being significantly more potent. More specifically, the three HFRs up-regulated genes related to cell cycle and FGF10 signaling, at late stages of the hepatic differentiation. This indicates the three chemicals promoted hepatoblast proliferation likely via up-regulating the FGF10 cascade. At the same time, we also presented a powerful way to combine in vitro differentiation and in silico transcriptomic analyses, to efficiently evaluate hazardous materials’ adverse effects on lineage fate decisions during early development.
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