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. 2018 Oct 29:2018:8608327.
doi: 10.1155/2018/8608327. eCollection 2018.

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

Guizhen Du  1   2   3 , Mingming Yu  1   2 , Lingling Wang  1   2 , Weiyue Hu  1   2 , Ling Song  1   2 , Chuncheng Lu  1   2   3 , Xinru Wang  1   2   3
Affiliations

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

Guizhen Du et al. Stem Cells Int. .

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.

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Figures

Figure 1
Figure 1
Structural characterization of H9-derived CMs. CMs were generated from H9 hESCs using the monolayer-based directed differentiation protocol. At day 20, CMs were immunostained for α-actinin (red) and cTnT (green). The cell nuclei were stained with DAPI (blue). Scale bar = 50 μm.
Figure 2
Figure 2
Quantitative analysis of CMs differentiated from hESCs. (a) Effect of TCS on cardiac differentiation. NKX2.5 expression in H9-derived CMs in the TCS-treated and the control groups was assessed and quantified. Data are expressed as average percentage of the positive area in each group. Error bars represent SEM. ∗ represents statistical significance (p < 0.05). (b) The spontaneous beating rates of CMs were counted. Data were analyzed from three independent experiments. Error bars represent SEM. ∗ p < 0.05.
Figure 3
Figure 3
TCS exposure altered CM transcriptome. (a) Heatmap of differential expressed genes in the TCS and control groups. (b) Volcano plot of differential expressed genes in the TCS and control groups. (c) UCSC genome browser of DEGs. (d) GO analysis of differential methylated regions in TCS and control groups.
Figure 4
Figure 4
TCS shaped DNA methylation pattern in CMs. (a) Circos plot of DNA methylation levels in the TCS and control groups. (b) Heatmap of differential methylated regions in the TCS and control groups. (c) The underlying DNA sequences of DMRs are conserved across placental mammals. (d) Genome distribution of DMRs. (e) Motif analysis of DMRs. (f) GO analysis of DMRs.
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