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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| Format: | Article |
| Language: | English |
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MDPI AG
2019-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/2/192 |
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| author | Georg Tascher Audrey Burban Sandrine Camus Marine Plumel Stéphanie Chanon Remy Le Guevel Valery Shevchenko Alain Van Dorsselaer Etienne Lefai Christiane Guguen-Guillouzo Fabrice Bertile |
| author_facet | Georg Tascher Audrey Burban Sandrine Camus Marine Plumel Stéphanie Chanon Remy Le Guevel Valery Shevchenko Alain Van Dorsselaer Etienne Lefai Christiane Guguen-Guillouzo Fabrice Bertile |
| author_sort | Georg Tascher |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-12T20:13:55Z |
| format | Article |
| id | doaj.art-bf6ee72a9e84431a80f1e7b1a3047602 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T20:13:55Z |
| publishDate | 2019-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-bf6ee72a9e84431a80f1e7b1a30476022023-08-02T01:28:53ZengMDPI AGCells2073-44092019-02-018219210.3390/cells8020192cells8020192In-Depth Proteome Analysis Highlights HepaRG Cells as a Versatile Cell System Surrogate for Primary Human HepatocytesGeorg Tascher0Audrey Burban1Sandrine Camus2Marine Plumel3Stéphanie Chanon4Remy Le Guevel5Valery Shevchenko6Alain Van Dorsselaer7Etienne Lefai8Christiane Guguen-Guillouzo9Fabrice Bertile10Laboratoire de Spectrométrie de Masse BioOrganique, CNRS, IPHC UMR 7178, Université de Strasbourg, F-67087 Strasbourg, FranceINSERM U1241 NuMeCan, Université de Rennes 1, F-35033 Rennes, FranceBiopredic International, Parc d’Affaires de la Bretêche, F-35760 St Grégoire, FranceLaboratoire de Spectrométrie de Masse BioOrganique, CNRS, IPHC UMR 7178, Université de Strasbourg, F-67087 Strasbourg, FranceCarMeN Laboratory, INSERM, INRA, University of Lyon, F-69310 Pierre-Bénite, FranceImPACcell platform, Biosit, Université de Rennes 1, F-35043 Rennes, FranceBiopredic International, Parc d’Affaires de la Bretêche, F-35760 St Grégoire, FranceLaboratoire de Spectrométrie de Masse BioOrganique, CNRS, IPHC UMR 7178, Université de Strasbourg, F-67087 Strasbourg, FranceCarMeN Laboratory, INSERM, INRA, University of Lyon, F-69310 Pierre-Bénite, FranceINSERM U1241 NuMeCan, Université de Rennes 1, F-35033 Rennes, FranceLaboratoire de Spectrométrie de Masse BioOrganique, CNRS, IPHC UMR 7178, Université de Strasbourg, F-67087 Strasbourg, FranceOf 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.https://www.mdpi.com/2073-4409/8/2/192Hepatocytesliver cell linesHepaRG cellsproteomesecretomehepatic phenotypedetoxificationliver metabolismliver diseasestransdifferentiation |
| spellingShingle | Georg Tascher Audrey Burban Sandrine Camus Marine Plumel Stéphanie Chanon Remy Le Guevel Valery Shevchenko Alain Van Dorsselaer Etienne Lefai Christiane Guguen-Guillouzo Fabrice Bertile In-Depth Proteome Analysis Highlights HepaRG Cells as a Versatile Cell System Surrogate for Primary Human Hepatocytes Cells Hepatocytes liver cell lines HepaRG cells proteome secretome hepatic phenotype detoxification liver metabolism liver diseases transdifferentiation |
| 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 | Hepatocytes liver cell lines HepaRG cells proteome secretome hepatic phenotype detoxification liver metabolism liver diseases transdifferentiation |
| url | https://www.mdpi.com/2073-4409/8/2/192 |
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