Transcriptional and Epigenetic Consequences of DMSO Treatment on HepaRG Cells.
Hélène Dubois-Pot-SchneiderCaroline AninatKathrin KattlerKarim FekirKathleen JarnouenVirginie CerecDenise GlaiseAbdulrahman SalhabGilles GasparoniKubo TakashiSeiichi IshidaJörn WalterAnne CorluPublished in: Cells (2022)
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.
Keyphrases
- gene expression
- induced apoptosis
- dna methylation
- cell cycle arrest
- genome wide
- endoplasmic reticulum stress
- oxidative stress
- signaling pathway
- emergency department
- cell death
- endothelial cells
- type diabetes
- metabolic syndrome
- cell proliferation
- liver injury
- genome wide identification
- inflammatory response
- smoking cessation
- combination therapy
- fatty acid
- pluripotent stem cells