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Global Gene Expression Profiling Reveals Isorhamnetin Induces Hepatic-Lineage Specific Differentiation in Human Amniotic Epithelial Cells

Human amnion epithelial cells (hAECs), derived from discarded term placenta, is anticipated as a new stem cell resource because of their advantages over embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), such as no risk of tumorigenicity and minimal ethical issue. hAECs have bee...

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Autores principales: Uchida, Yoshiaki, Ferdousi, Farhana, Zheng, Yun-Wen, Oda, Tatsuya, Isoda, Hiroko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674172/
https://www.ncbi.nlm.nih.gov/pubmed/33224947
http://dx.doi.org/10.3389/fcell.2020.578036
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author Uchida, Yoshiaki
Ferdousi, Farhana
Zheng, Yun-Wen
Oda, Tatsuya
Isoda, Hiroko
author_facet Uchida, Yoshiaki
Ferdousi, Farhana
Zheng, Yun-Wen
Oda, Tatsuya
Isoda, Hiroko
author_sort Uchida, Yoshiaki
collection PubMed
description Human amnion epithelial cells (hAECs), derived from discarded term placenta, is anticipated as a new stem cell resource because of their advantages over embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), such as no risk of tumorigenicity and minimal ethical issue. hAECs have been reported to differentiate into hepatic-like cells (HLCs) with variable functionalities suitable for cell-based therapy of end-stage liver diseases, drug screening, and drug toxicity tests. On the other hand, a new research stream has been evolving to use natural compounds as stimulants of stem cell differentiation because of their high availability and minimum side effects. Isorhamnetin is a naturally occurring flavonoid commonly found in fruits and vegetables and has been reported to improve hepatic fibrosis and steatosis. In this present study, we have screened the differentiation potential of isorhamnetin in hAECs. The cells were grown on 3D cell culture and were treated with 20 μM of synthesized isorhamnetin for 10 days without adding any additional growth factors. DNA microarray global gene expression analysis was conducted for differentially expressed genes between isorhamnetin-treated and untreated control cells, gene expression validation was carried out using RT-qPCR method, and finally, several hepatic functions were assessed. Microarray analysis showed that isorhamnetin could activate essential biological processes, molecular functions, and signaling pathways for hepatic differentiation. Hepatic progenitor markers, EPCAM and DLK1, were upregulated in the isorhamnetin-treated hAECs. AFP was downregulated, while ALB was upregulated on Day 10. Furthermore, isorhamnetin-treated cells could show increased CYP enzyme mRNA levels, ICG uptake and release, glycogen storage activity, and urea secretion. Additionally, isorhamnetin-treated cells did not show any trace of transdifferentiation evident by significant downregulation of several colon- and cholangiocyte-specific markers. However, longer treatment with isorhamnetin did not promote hepatic maturation. Altogether, our findings indicate that isorhamnetin has a promising effect on directing the hepatic-lineage specific differentiation in hAECs.
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spelling pubmed-76741722020-11-19 Global Gene Expression Profiling Reveals Isorhamnetin Induces Hepatic-Lineage Specific Differentiation in Human Amniotic Epithelial Cells Uchida, Yoshiaki Ferdousi, Farhana Zheng, Yun-Wen Oda, Tatsuya Isoda, Hiroko Front Cell Dev Biol Cell and Developmental Biology Human amnion epithelial cells (hAECs), derived from discarded term placenta, is anticipated as a new stem cell resource because of their advantages over embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), such as no risk of tumorigenicity and minimal ethical issue. hAECs have been reported to differentiate into hepatic-like cells (HLCs) with variable functionalities suitable for cell-based therapy of end-stage liver diseases, drug screening, and drug toxicity tests. On the other hand, a new research stream has been evolving to use natural compounds as stimulants of stem cell differentiation because of their high availability and minimum side effects. Isorhamnetin is a naturally occurring flavonoid commonly found in fruits and vegetables and has been reported to improve hepatic fibrosis and steatosis. In this present study, we have screened the differentiation potential of isorhamnetin in hAECs. The cells were grown on 3D cell culture and were treated with 20 μM of synthesized isorhamnetin for 10 days without adding any additional growth factors. DNA microarray global gene expression analysis was conducted for differentially expressed genes between isorhamnetin-treated and untreated control cells, gene expression validation was carried out using RT-qPCR method, and finally, several hepatic functions were assessed. Microarray analysis showed that isorhamnetin could activate essential biological processes, molecular functions, and signaling pathways for hepatic differentiation. Hepatic progenitor markers, EPCAM and DLK1, were upregulated in the isorhamnetin-treated hAECs. AFP was downregulated, while ALB was upregulated on Day 10. Furthermore, isorhamnetin-treated cells could show increased CYP enzyme mRNA levels, ICG uptake and release, glycogen storage activity, and urea secretion. Additionally, isorhamnetin-treated cells did not show any trace of transdifferentiation evident by significant downregulation of several colon- and cholangiocyte-specific markers. However, longer treatment with isorhamnetin did not promote hepatic maturation. Altogether, our findings indicate that isorhamnetin has a promising effect on directing the hepatic-lineage specific differentiation in hAECs. Frontiers Media S.A. 2020-11-05 /pmc/articles/PMC7674172/ /pubmed/33224947 http://dx.doi.org/10.3389/fcell.2020.578036 Text en Copyright © 2020 Uchida, Ferdousi, Zheng, Oda and Isoda. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Uchida, Yoshiaki
Ferdousi, Farhana
Zheng, Yun-Wen
Oda, Tatsuya
Isoda, Hiroko
Global Gene Expression Profiling Reveals Isorhamnetin Induces Hepatic-Lineage Specific Differentiation in Human Amniotic Epithelial Cells
title Global Gene Expression Profiling Reveals Isorhamnetin Induces Hepatic-Lineage Specific Differentiation in Human Amniotic Epithelial Cells
title_full Global Gene Expression Profiling Reveals Isorhamnetin Induces Hepatic-Lineage Specific Differentiation in Human Amniotic Epithelial Cells
title_fullStr Global Gene Expression Profiling Reveals Isorhamnetin Induces Hepatic-Lineage Specific Differentiation in Human Amniotic Epithelial Cells
title_full_unstemmed Global Gene Expression Profiling Reveals Isorhamnetin Induces Hepatic-Lineage Specific Differentiation in Human Amniotic Epithelial Cells
title_short Global Gene Expression Profiling Reveals Isorhamnetin Induces Hepatic-Lineage Specific Differentiation in Human Amniotic Epithelial Cells
title_sort global gene expression profiling reveals isorhamnetin induces hepatic-lineage specific differentiation in human amniotic epithelial cells
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674172/
https://www.ncbi.nlm.nih.gov/pubmed/33224947
http://dx.doi.org/10.3389/fcell.2020.578036
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