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三氯生诱导心肌细胞分化毒性过程中的转录组和DNA甲基化组动态变化

Transcriptome and DNA Methylome Dynamics during Triclosan-Induced Cardiomyocyte Differentiation Toxicity.

作者信息

Du Guizhen, Yu Mingming, Wang Lingling, Hu Weiyue, Song Ling, Lu Chuncheng, Wang Xinru

机构信息

State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.

Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.

出版信息

Stem Cells Int. 2018 Oct 29;2018:8608327. doi: 10.1155/2018/8608327. eCollection 2018.

Abstract

Cardiac development is a dynamic process and sensitive to environmental chemicals. Triclosan is widely used as an antibacterial agent and reported to transport across the placenta and affect embryonic development. Here, we used human embryonic stem cell- (hESC-) derived cardiomyocytes (CMs) to determine the effects of TCS exposure on cardiac development. After TCS treatment, the differentiation process was significantly blocked and spontaneous beating rates of CMs were also decreased. Transcriptome analysis showed the dysregulation of genes involved in cardiogenesis, including GATA4 and TNNT2. Additionally, DNA methylation was also altered by TCS exposure, especially in those regions with GATA motif enrichment. These alterations of transcriptome and DNA methylation were all associated with signaling pathways integral to heart development. Our findings indicate that TCS exposure might cause cardiomyocyte differentiation toxicity and provide the new insights into how environmental factors regulate DNA methylation and gene expressions during heart development.

摘要

心脏发育是一个动态过程,对环境化学物质敏感。三氯生作为一种抗菌剂被广泛使用,据报道它可穿过胎盘并影响胚胎发育。在此,我们使用人胚胎干细胞(hESC)来源的心肌细胞(CMs)来确定三氯生暴露对心脏发育的影响。三氯生处理后,分化过程明显受阻,CMs的自发搏动率也降低。转录组分析显示参与心脏发生的基因失调,包括GATA4和TNNT2。此外,三氯生暴露也改变了DNA甲基化,特别是在富含GATA基序的区域。转录组和DNA甲基化的这些改变均与心脏发育不可或缺的信号通路相关。我们的研究结果表明,三氯生暴露可能导致心肌细胞分化毒性,并为环境因素如何在心脏发育过程中调节DNA甲基化和基因表达提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69e5/6231387/8f667b165637/SCI2018-8608327.001.jpg

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