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

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...

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Autores principales: Tascher, Georg, Burban, Audrey, Camus, Sandrine, Plumel, Marine, Chanon, Stéphanie, Le Guevel, Remy, Shevchenko, Valery, Van Dorsselaer, Alain, Lefai, Etienne, Guguen-Guillouzo, Christiane, Bertile, Fabrice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406872/
https://www.ncbi.nlm.nih.gov/pubmed/30795634
http://dx.doi.org/10.3390/cells8020192
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author Tascher, Georg
Burban, Audrey
Camus, Sandrine
Plumel, Marine
Chanon, Stéphanie
Le Guevel, Remy
Shevchenko, Valery
Van Dorsselaer, Alain
Lefai, Etienne
Guguen-Guillouzo, Christiane
Bertile, Fabrice
author_facet Tascher, Georg
Burban, Audrey
Camus, Sandrine
Plumel, Marine
Chanon, Stéphanie
Le Guevel, Remy
Shevchenko, Valery
Van Dorsselaer, Alain
Lefai, Etienne
Guguen-Guillouzo, Christiane
Bertile, Fabrice
author_sort Tascher, Georg
collection PubMed
description 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.
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spelling pubmed-64068722019-03-19 In-Depth Proteome Analysis Highlights HepaRG Cells as a Versatile Cell System Surrogate for Primary Human Hepatocytes Tascher, Georg Burban, Audrey Camus, Sandrine Plumel, Marine Chanon, Stéphanie Le Guevel, Remy Shevchenko, Valery Van Dorsselaer, Alain Lefai, Etienne Guguen-Guillouzo, Christiane Bertile, Fabrice Cells Article 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. MDPI 2019-02-21 /pmc/articles/PMC6406872/ /pubmed/30795634 http://dx.doi.org/10.3390/cells8020192 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tascher, Georg
Burban, Audrey
Camus, Sandrine
Plumel, Marine
Chanon, Stéphanie
Le Guevel, Remy
Shevchenko, Valery
Van Dorsselaer, Alain
Lefai, Etienne
Guguen-Guillouzo, Christiane
Bertile, Fabrice
In-Depth Proteome Analysis Highlights HepaRG Cells as a Versatile Cell System Surrogate for Primary Human Hepatocytes
title In-Depth Proteome Analysis Highlights HepaRG Cells as a Versatile Cell System Surrogate for Primary Human Hepatocytes
title_full In-Depth Proteome Analysis Highlights HepaRG Cells as a Versatile Cell System Surrogate for Primary Human Hepatocytes
title_fullStr In-Depth Proteome Analysis Highlights HepaRG Cells as a Versatile Cell System Surrogate for Primary Human Hepatocytes
title_full_unstemmed In-Depth Proteome Analysis Highlights HepaRG Cells as a Versatile Cell System Surrogate for Primary Human Hepatocytes
title_short In-Depth Proteome Analysis Highlights HepaRG Cells as a Versatile Cell System Surrogate for Primary Human Hepatocytes
title_sort in-depth proteome analysis highlights heparg cells as a versatile cell system surrogate for primary human hepatocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406872/
https://www.ncbi.nlm.nih.gov/pubmed/30795634
http://dx.doi.org/10.3390/cells8020192
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