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

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...

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Autores principales: Kim, Dae‐Soo, Ryu, Jea‐Woon, Son, Mi‐Young, Oh, Jung‐Hwa, Chung, Kyung‐Sook, Lee, Sugi, Lee, Jeong‐Ju, Ahn, Jun‐Ho, Min, Ju‐Sik, Ahn, Jiwon, Kang, Hyun Mi, Kim, Janghwan, Jung, Cho‐Rok, Kim, Nam‐Soon, Cho, Hyun‐Soo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698781/
https://www.ncbi.nlm.nih.gov/pubmed/28640507
http://dx.doi.org/10.1002/hep.29324
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author Kim, Dae‐Soo
Ryu, Jea‐Woon
Son, Mi‐Young
Oh, Jung‐Hwa
Chung, Kyung‐Sook
Lee, Sugi
Lee, Jeong‐Ju
Ahn, Jun‐Ho
Min, Ju‐Sik
Ahn, Jiwon
Kang, Hyun Mi
Kim, Janghwan
Jung, Cho‐Rok
Kim, Nam‐Soon
Cho, Hyun‐Soo
author_facet Kim, Dae‐Soo
Ryu, Jea‐Woon
Son, Mi‐Young
Oh, Jung‐Hwa
Chung, Kyung‐Sook
Lee, Sugi
Lee, Jeong‐Ju
Ahn, Jun‐Ho
Min, Ju‐Sik
Ahn, Jiwon
Kang, Hyun Mi
Kim, Janghwan
Jung, Cho‐Rok
Kim, Nam‐Soon
Cho, Hyun‐Soo
author_sort Kim, Dae‐Soo
collection PubMed
description 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).
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spelling pubmed-56987812017-11-30 A liver‐specific gene expression panel predicts the differentiation status of in vitro hepatocyte models Kim, Dae‐Soo Ryu, Jea‐Woon Son, Mi‐Young Oh, Jung‐Hwa Chung, Kyung‐Sook Lee, Sugi Lee, Jeong‐Ju Ahn, Jun‐Ho Min, Ju‐Sik Ahn, Jiwon Kang, Hyun Mi Kim, Janghwan Jung, Cho‐Rok Kim, Nam‐Soon Cho, Hyun‐Soo Hepatology Original Articles 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). John Wiley and Sons Inc. 2017-10-03 2017-11 /pmc/articles/PMC5698781/ /pubmed/28640507 http://dx.doi.org/10.1002/hep.29324 Text en © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Kim, Dae‐Soo
Ryu, Jea‐Woon
Son, Mi‐Young
Oh, Jung‐Hwa
Chung, Kyung‐Sook
Lee, Sugi
Lee, Jeong‐Ju
Ahn, Jun‐Ho
Min, Ju‐Sik
Ahn, Jiwon
Kang, Hyun Mi
Kim, Janghwan
Jung, Cho‐Rok
Kim, Nam‐Soon
Cho, Hyun‐Soo
A liver‐specific gene expression panel predicts the differentiation status of in vitro hepatocyte models
title A liver‐specific gene expression panel predicts the differentiation status of in vitro hepatocyte models
title_full A liver‐specific gene expression panel predicts the differentiation status of in vitro hepatocyte models
title_fullStr A liver‐specific gene expression panel predicts the differentiation status of in vitro hepatocyte models
title_full_unstemmed A liver‐specific gene expression panel predicts the differentiation status of in vitro hepatocyte models
title_short A liver‐specific gene expression panel predicts the differentiation status of in vitro hepatocyte models
title_sort liver‐specific gene expression panel predicts the differentiation status of in vitro hepatocyte models
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698781/
https://www.ncbi.nlm.nih.gov/pubmed/28640507
http://dx.doi.org/10.1002/hep.29324
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