Dataset Information

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

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.

SUBMITTER: Du G

PROVIDER: S-EPMC6231387 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Du Guizhen G Yu Mingming M Wang Lingling L Hu Weiyue W Song Ling L Lu Chuncheng C Wang Xinru X

Stem cells international 20181029

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. Transcript ...[more]

PMID: 30510588

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Project description:BackgroundPekin duck is an important animal model for its ability for fat synthesis and deposition. However, transcriptional dynamic regulation of adipose differentiation driven by complex signal cascades remains largely unexplored in this model. This study aimed to explore adipogenic transcriptional dynamics before (proliferation) and after (differentiation) initial preadipocyte differentiation in ducks.ResultsExogenous oleic acid alone successfully induced duck subcutaneous preadipocyte differentiation. We explored 36 mRNA-seq libraries in order to study transcriptome dynamics during proliferation and differentiation processes at 6 time points. Using robust statistical analysis, we identified 845, 652, 359, 2401 and 1933 genes differentially expressed between -48 h and 0 h, 0 h and 12 h, 12 h and 24 h, 24 h and 48 h, 48 h and 72 h, respectively (FDR < 0.05, FC > 1.5). At the proliferation stage, proliferation related pathways and basic cellular and metabolic processes were inhibited, while regulatory factors that initiate differentiation enter the ready-to-activate state, which provides a precondition for initiating adipose differentiation. According to weighted gene co-expression network analysis, pathways positively related to adipogenic differentiation are significantly activated at the differentiation stage, while WNT, FOXO and other pathways that inhibit preadipocyte differentiation are negatively regulated. Moreover, we identified and classified more than 100 transcription factors that showed significant changes during differentiation, and found novel transcription factors that were not reported to be related to preadipoctye differentiation. Finally, we manually assembled a proposed regulation network model of subcutaneous preadipocyte differentiation base on the expression data, and suggested that E2F1 may serve as an important link between the processes of duck subcutaneous preadipocyte proliferation and differentiation.ConclusionsFor the first time we comprehensively analyzed the transcriptome dynamics of duck subcutaneous preadipocyte proliferation and differentiation. The current study provides a solid basis for understanding the synthesis and deposition of subcutaneous fat in ducks. Furthermore, the information generated will allow future investigations of specific genes involved in particular stages of duck adipogenesis.

Dataset Information

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

Publications

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

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