Journal
CELLS
Volume 11, Issue 15, Pages -Publisher
MDPI
DOI: 10.3390/cells11152298
Keywords
DMSO; HepaRG cells; hepatic differentiation; gene expression; histone modification
Categories
Funding
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Centre National de la Recherche Scientifique (CNRS)
- University of Rennes
- INSERM/Japan Society for the Promotion of Science cooperation programme
- Seventh Framework Programme (FP7) LIV-ES [223317]
- Contrat Plan Etat Region
- Conseil Regional de Bretagne
- EU [FP7 267038]
- German Federal Ministry of Education and Research (BMBF) [01EK1604A-D]
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DMSO influences liver-specific gene expression and regulates gene expression through multiple regulatory factors, as well as histone acetylation and deacetylation. Additionally, there is an interplay between cytoskeleton organization and extracellular matrix remodeling with hepatocyte maturation.
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 PPAR alpha whereas genes not affected by this addition are regulated by HNF1 alpha, HNF4 alpha, and PPAR alpha. 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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