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Embryonic germ cell extracts erase imprinted genes and improve the efficiency of induced pluripotent stem cells

Patient-specific induced pluripotent stem cells (iPSCs) have the potential to be useful in the treatment of human diseases. While prior studies have reported multiple methods to generate iPSCs, DNA methylation continues to limit the totipotency and reprogramming efficiency of iPSCs. Here, we first s...

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Autores principales: Hu, Jing, Zhao, Qiaoshi, Feng, Yukuan, Li, Na, Gu, Yanli, Sun, Ruizhen, Duan, Lian, Wu, Yanshuang, Shan, Zhiyan, Lei, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053380/
https://www.ncbi.nlm.nih.gov/pubmed/30026469
http://dx.doi.org/10.1038/s41598-018-29339-0
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author Hu, Jing
Zhao, Qiaoshi
Feng, Yukuan
Li, Na
Gu, Yanli
Sun, Ruizhen
Duan, Lian
Wu, Yanshuang
Shan, Zhiyan
Lei, Lei
author_facet Hu, Jing
Zhao, Qiaoshi
Feng, Yukuan
Li, Na
Gu, Yanli
Sun, Ruizhen
Duan, Lian
Wu, Yanshuang
Shan, Zhiyan
Lei, Lei
author_sort Hu, Jing
collection PubMed
description Patient-specific induced pluripotent stem cells (iPSCs) have the potential to be useful in the treatment of human diseases. While prior studies have reported multiple methods to generate iPSCs, DNA methylation continues to limit the totipotency and reprogramming efficiency of iPSCs. Here, we first show the competency of embryonic germ cells (EGCs) as a reprogramming catalyst capable of effectively promoting reprogramming induced by four defined factors, including Oct4, Sox2, Klf4 and c-Myc. Combining EGC extracts with these four factors resulted in formation of more embryonic stem cell-like colonies than did factors alone. Notably, expression of imprinted genes was higher with combined induction than with factors alone. Moreover, iPSCs derived from the combined inductors tended to have more global hypomethylation. Our research not only provides evidence that EGC extracts could activate DNA demethylation and reprogram imprinted genes, but also establishes a new way to enhance reprogramming of iPSCs, which remains a critical safety concern for potential use of iPSCs in regenerative medicine.
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spelling pubmed-60533802018-07-23 Embryonic germ cell extracts erase imprinted genes and improve the efficiency of induced pluripotent stem cells Hu, Jing Zhao, Qiaoshi Feng, Yukuan Li, Na Gu, Yanli Sun, Ruizhen Duan, Lian Wu, Yanshuang Shan, Zhiyan Lei, Lei Sci Rep Article Patient-specific induced pluripotent stem cells (iPSCs) have the potential to be useful in the treatment of human diseases. While prior studies have reported multiple methods to generate iPSCs, DNA methylation continues to limit the totipotency and reprogramming efficiency of iPSCs. Here, we first show the competency of embryonic germ cells (EGCs) as a reprogramming catalyst capable of effectively promoting reprogramming induced by four defined factors, including Oct4, Sox2, Klf4 and c-Myc. Combining EGC extracts with these four factors resulted in formation of more embryonic stem cell-like colonies than did factors alone. Notably, expression of imprinted genes was higher with combined induction than with factors alone. Moreover, iPSCs derived from the combined inductors tended to have more global hypomethylation. Our research not only provides evidence that EGC extracts could activate DNA demethylation and reprogram imprinted genes, but also establishes a new way to enhance reprogramming of iPSCs, which remains a critical safety concern for potential use of iPSCs in regenerative medicine. Nature Publishing Group UK 2018-07-19 /pmc/articles/PMC6053380/ /pubmed/30026469 http://dx.doi.org/10.1038/s41598-018-29339-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hu, Jing
Zhao, Qiaoshi
Feng, Yukuan
Li, Na
Gu, Yanli
Sun, Ruizhen
Duan, Lian
Wu, Yanshuang
Shan, Zhiyan
Lei, Lei
Embryonic germ cell extracts erase imprinted genes and improve the efficiency of induced pluripotent stem cells
title Embryonic germ cell extracts erase imprinted genes and improve the efficiency of induced pluripotent stem cells
title_full Embryonic germ cell extracts erase imprinted genes and improve the efficiency of induced pluripotent stem cells
title_fullStr Embryonic germ cell extracts erase imprinted genes and improve the efficiency of induced pluripotent stem cells
title_full_unstemmed Embryonic germ cell extracts erase imprinted genes and improve the efficiency of induced pluripotent stem cells
title_short Embryonic germ cell extracts erase imprinted genes and improve the efficiency of induced pluripotent stem cells
title_sort embryonic germ cell extracts erase imprinted genes and improve the efficiency of induced pluripotent stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053380/
https://www.ncbi.nlm.nih.gov/pubmed/30026469
http://dx.doi.org/10.1038/s41598-018-29339-0
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