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

Cells
Georg TascherFabrice Bertile

Abstract

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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Citations

Sep 29, 2020·Journal of Toxicology and Environmental Health. Part a·Xiaoqing GuoNan Mei
Jul 7, 2019·Viruses·Rebecca Menhua FuViet Loan Dao Thi
May 20, 2020·International Journal of Molecular Sciences·Juliette LeglerJorke H Kamstra

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Datasets Mentioned

BETA
PXD010304

Methods Mentioned

BETA
FCS
protein assay
electrophoresis
chip
bioprinting
enzyme-linked immunosorbent assay

Software Mentioned

R Foundation for Statistical Computing
MaxQuant
OtofControl
Perseus
SecretomeP
MSDA
R
IPA
Hystar
Data Analysis

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