A liver-specific gene expression panel predicts the differentiation status of In vitro hepatocyte models

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Title
A liver-specific gene expression panel predicts the differentiation status of In vitro hepatocyte models
Author(s)
Dae Soo Kim; Jea Woon Ryu; Mi Young Son; J H Oh; Kyung-Sook Chung; Sugi Lee; Jeong Ju Lee; Jun Ho Ahn; Ju-Sik Min; Jiwon AhnHyun Mi KangJanghwan KimCho Rok JungNam-Soon KimHyun Soo Cho
Bibliographic Citation
Hepatology, vol. 66, no. 5, pp. 1662-1674
Publication Year
2017
Abstract
Alternative cell sources, such as three-dimensional organoids and induced pluripotent stem cell?derived cells, might provide a potentially effective approach for both drug development applications and clinical transplantation. For example, the development of cell sources for liver cell?based therapy has been increasingly needed, and liver transplantation is performed for the treatment for patients with severe end-stage liver disease. Differentiated liver cells and three-dimensional organoids are expected to provide new cell sources for tissue models and revolutionary clinical therapies. However, conventional experimental methods confirming the expression levels of liver-specific lineage markers cannot provide complete information regarding the differentiation status or degree of similarity between liver and differentiated cell sources. Therefore, in this study, to overcome several issues associated with the assessment of differentiated liver cells and organoids, we developed a liver-specific gene expression panel (LiGEP) algorithm that presents the degree of liver similarity as a “percentage.” We demonstrated that the percentage calculated using the LiGEP algorithm was correlated with the developmental stages of in vivo liver tissues in mice, suggesting that LiGEP can correctly predict developmental stages. Moreover, three-dimensional cultured HepaRG cells and human pluripotent stem cell?derived hepatocyte-like cells showed liver similarity scores of 59.14% and 32%, respectively, although general liver-specific markers were detected. Conclusion: Our study describes a quantitative and predictive model for differentiated samples, particularly liver-specific cells or organoids; and this model can be further expanded to various tissue-specific organoids; our LiGEP can provide useful information and insights regarding the differentiation status of in vitro liver models. (Hepatology 2017;66:1662?1674).
ISSN
0270-9139
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/hep.29324
Type
Article
Appears in Collections:
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
Division of Research on National Challenges > 1. Journal Articles
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
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