Fiche publication


Date publication

juillet 2022

Journal

Cells

Auteurs

Membres identifiés du Cancéropôle Est :
Dr DUBOIS-POT-SCHNEIDER Hélène


Tous les auteurs :
Dubois-Pot-Schneider H, Aninat C, Kattler K, Fekir K, Jarnouen K, Cerec V, Glaise D, Salhab A, Gasparoni G, Takashi K, Ishida S, Walter J, Corlu A

Résumé

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.

Mots clés

DMSO, HepaRG cells, gene expression, hepatic differentiation, histone modification

Référence

Cells. 2022 07 26;11(15):