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Epigenetic consequences of DMSO treatment on the HepaRG cell line

ABSTRACT: Epigenetic consequences of DMSO treatment on the HepaRG cell line

PROVIDER: PRJNA746146 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15115761_1.fastq.gz	Fastqsanger.gz
	SRR15115761_2.fastq.gz	Fastqsanger.gz
	SRR15115762_1.fastq.gz	Fastqsanger.gz
	SRR15115762_2.fastq.gz	Fastqsanger.gz
	SRR15115763_1.fastq.gz	Fastqsanger.gz

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Epigenetic consequences of DMSO treatment on the HepaRG cell line

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Transcriptional and Epigenetic Consequences of DMSO Treatment on HepaRG Cells.

Project description:Dimethyl sulfoxide (DMSO) is used to sustain or favor hepatocyte differentiation in vitro. Thus, DMSO is used in the differentiation protocol of the HepaRG cells that present the closest drug-metabolizing enzyme activities to primary human hepatocytes in culture. The aim of our study is to clarify its influence on liver-specific gene expression. For that purpose, we performed a large-scale analysis (gene expression and histone modification) to determine the global role of DMSO exposure during the differentiation process of the HepaRG cells. The addition of DMSO drives the upregulation of genes mainly regulated by PXR and PPARα whereas genes not affected by this addition are regulated by HNF1α, HNF4α, and PPARα. DMSO-differentiated-HepaRG cells show a differential expression for genes regulated by histone acetylation, while differentiated-HepaRG cells without DMSO show gene signatures associated with histone deacetylases. In addition, we observed an interplay between cytoskeleton organization and EMC remodeling with hepatocyte maturation.

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DMSO effect on HepaRG differentiation

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Project description:Gene expression profile analysis allowed to identify a panel of genes characteristic of HepaRG differentiation and DMSO effect on the differentiation process.

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Project description:Comparison of expression profiles detected inundifferemtitated HepaRG cells exposed to DMSO, TCDD for 24h. The aryl hydrocarbon receptor (AhR) activation has been shown to stimulate proliferation, promote apoptosis or alter differentiation of adult rat liver progenitors. We investigated the impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated AhR activation on a human model of bipotent liver progenitors, undifferentiated HepaRG cells. We used both intact undifferentiated HepaRG cells, and HepaRG cells with silenced Hippo pathway effectors, YAP1 and TAZ, which play key role(s) in tissue specific progenitor cell self-renewal and expansion, including liver, cardiac or respiratory progenitors.

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Project description:The aim of the study was to characterize at a molecular level (changes in mRNA level) the effects of WNT3A on the human HepaRG hepatocellular carcinoma cell line. This was adressed by culturing HepaRG cells in presence or absence of Wnt3a.

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Project description:The exposure to and contamination by Persistent Organic Pollutants (POPs), which include pesticides used worldwide and polyaromatic hydrocarbons, is detrimental to human health and diverse ecosystems. Although most mechanistic studies have focused on single compounds, living organisms are exposed to multiple environmental xenobiotics, simultaneously, throughout their lives. The experimental evidence useful for assessing the effects of exposure to pollutant mixtures is scarce. We investigated the effects of exposure to a combination of two POPs, which employ different xenosensors, on global gene expression in a human hepatocyte cell model, HepaRG. Whole genome microarrays were used to investigate the effects on the HepaRG transcriptome following exposure to the combination of POPs as compared to each compound individually. Differentiated HepaRG cells were treated with either 2,3,7,8 tetrachlorodibenzo-p-dioxin, alpha-endosulfan (an organochlorine pesticide), the mixture or the DMSO vehicle for 30 hours after which RNA was extracted for hybridization on Affymetrix whole human genome microarrays.

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