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Hepatology. 2017 Nov;66(5):1662-1674. doi: 10.1002/hep.29324. Epub 2017 Oct 3.

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

Kim DS1,2, Ryu JW1, Son MY2,3, Oh JH4, Chung KS1,2, Lee S1,2, Lee JJ1, Ahn JH1, Min JS1, Ahn J1, Kang HM3, Kim J2,3, Jung CR2,3, Kim NS1,2, Cho HS1,2.

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Genome Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Department of Functional Genomics, Korea University of Science and Technology, Daejeon, Republic of Korea.
Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Korea Institute of Toxicology, Daejeon, Republic of Korea.


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.


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).

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