Establishment of a human embryonic stem cell-based liver differentiation model for hepatotoxicity evaluations
文献类型：期刊论文
| 作者 | Liang, Shengxian; Liang, Shaojun; Yin, Nuoya; Faiola, Francesco |
| 刊名 | ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
 |
| 出版日期 | 2019-06-15 |
| 卷号 | 174页码:353-362 |
| 关键词 | Thyroid hormones (THs) Polybrominated diphenyl ethers BDE-47/209 Human embryonic stem cells (ESCs) Developmental hepatotoxicity Endocrine-disrupting chemicals (EDCs) |
| ISSN号 | 0147-6513 |
| 英文摘要 | The liver is one of the major targets of hormones, including thyroid hormones (THs), and many industrial chemicals, such as endocrine-disrupting chemicals. Those compounds may permeate the placenta barrier and pose a risk for embryonic development. Therefore, it is necessary to assess the toxic effects of those kind of industrial chemicals during liver development. In this study, to mimic liver specification in vitro, we differentiated human embryonic stem cells (ESCs) into functional hepatocyte-like cells. We performed this differentiation process in presence of two THs, triiodothyronine (T3) and thyroxine (T4), with the purpose of identifying biomarkers for toxicity screening. TH exposure (3, 30 and 300 nM) yielded to hepatocytes with impaired glycogen storage ability and abnormal lipid droplets' accumulation. Global gene expression analysis by RNA-seq identified a number of genes responsible for hepatic differentiation and function which were affected by 30 nM T3 and T4. Those differentially expressed genes were used to assess the potential developmental liver toxicity of two famous environmental pollutants, 2, 2, 4, 4-tetrabromodiphenyl ether (BDE-47) and decabromodiphenyl ether (BDE-209), at 10 nM to 1 mu M treatments. Our findings demonstrate that BDE-47 and BDE-209, dysregulated pathways such as chemical carcinogenesis, steroid hormone biosynthesis and drug metabolism-cytochrome P450. Moreover, we were able to identify a set of 17 biomarkers, very useful to predict the potential developmental hepatotoxicity of industrial chemicals. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/42943]  |
| 专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
| 作者单位 | 1.Univ Chinese Acad Sci, Coll Resources & Environm, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liang, Shengxian,Liang, Shaojun,Yin, Nuoya,et al. Establishment of a human embryonic stem cell-based liver differentiation model for hepatotoxicity evaluations[J]. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY,2019,174:353-362. |
| APA | Liang, Shengxian,Liang, Shaojun,Yin, Nuoya,&Faiola, Francesco.(2019).Establishment of a human embryonic stem cell-based liver differentiation model for hepatotoxicity evaluations.ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY,174,353-362. |
| MLA | Liang, Shengxian,et al."Establishment of a human embryonic stem cell-based liver differentiation model for hepatotoxicity evaluations".ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 174(2019):353-362. |
入库方式： OAI收割
来源：生态环境研究中心
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