In-Depth Proteome Analysis Highlights HepaRG Cells as a Versatile Cell System Surrogate for Primary Human Hepatocytes

Cells

Sandrine Camus¹  Valery Shevchenko¹  Etienne Lefai²  Stéphanie Chanon²  Audrey Burban³  Christiane Guguen-Guillouzo³  Remy Le Guevel⁴  Georg Tascher⁵  Marine Plumel⁵  Alain Van Dorsselaer⁵  Fabrice Bertile⁵ 

[1] Biopredic International, Parc d’Affaires de la Bretêche, F-35760 St Grégoire, France;CarMeN Laboratory, INSERM, INRA, University of Lyon, F-69310 Pierre-Bénite, France;INSERM U1241 NuMeCan, Université de Rennes 1, F-35033 Rennes, France;ImPACcell platform, Biosit, Université de Rennes 1, F-35043 Rennes, France;Laboratoire de Spectrométrie de Masse BioOrganique, CNRS, IPHC UMR 7178, Université de Strasbourg, F-67087 Strasbourg, France;

关键词: Hepatocytes;    liver cell lines;    HepaRG cells;    proteome;    secretome;    hepatic phenotype;    detoxification;    liver metabolism;    liver diseases;    transdifferentiation;   

DOI  :  10.3390/cells8020192

来源: DOAJ

【 摘 要 】

Of the hepatic cell lines developed for in vitro studies of hepatic functions as alternatives to primary human hepatocytes, many have lost major liver-like functions, but not HepaRG cells. The increasing use of the latter worldwide raises the need for establishing the reference functional status of early biobanked HepaRG cells. Using deep proteome and secretome analyses, the levels of master regulators of the hepatic phenotype and of the structural elements ensuring biliary polarity were found to be close to those in primary hepatocytes. HepaRG cells proved to be highly differentiated, with functional mitochondria, hepatokine secretion abilities, and an adequate response to insulin. Among differences between primary human hepatocytes and HepaRG cells, the factors that possibly support HepaRG transdifferentiation properties are discussed. The HepaRG cell system thus appears as a robust surrogate for primary hepatocytes, which is versatile enough to study not only xenobiotic detoxification, but also the control of hepatic energy metabolism, secretory function and disease-related mechanisms.

【 授权许可】

Unknown