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Open AccessArticle

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

1
Laboratoire de Spectrométrie de Masse BioOrganique, CNRS, IPHC UMR 7178, Université de Strasbourg, F-67087 Strasbourg, France
2
Institute of Biochemistry II, Goethe University Hospital, D-60590 Frankfurt am Main, Germany
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INSERM U1241 NuMeCan, Université de Rennes 1, F-35033 Rennes, France
4
Biopredic International, Parc d’Affaires de la Bretêche, F-35760 St Grégoire, France
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CarMeN Laboratory, INSERM, INRA, University of Lyon, F-69310 Pierre-Bénite, France
6
ImPACcell platform, Biosit, Université de Rennes 1, F-35043 Rennes, France
*
Author to whom correspondence should be addressed.
Cells 2019, 8(2), 192; https://doi.org/10.3390/cells8020192
Received: 14 December 2018 / Revised: 16 February 2019 / Accepted: 18 February 2019 / Published: 21 February 2019
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. View Full-Text
Keywords: Hepatocytes; liver cell lines; HepaRG cells; proteome; secretome; hepatic phenotype; detoxification; liver metabolism; liver diseases; transdifferentiation Hepatocytes; liver cell lines; HepaRG cells; proteome; secretome; hepatic phenotype; detoxification; liver metabolism; liver diseases; transdifferentiation
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Tascher, G.; Burban, A.; Camus, S.; Plumel, M.; Chanon, S.; Le Guevel, R.; Shevchenko, V.; Van Dorsselaer, A.; Lefai, E.; Guguen-Guillouzo, C.; Bertile, F. In-Depth Proteome Analysis Highlights HepaRG Cells as a Versatile Cell System Surrogate for Primary Human Hepatocytes. Cells 2019, 8, 192.

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