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Reprogramming of fibroblast cells to totipotent state by DNA demethylation

Many attempts have been made to induce high-quality embryonic stem cells such as pluripotent stem cells and totipotent stem cells, but challenges remain to be overcome such as appropriate methods and sources. Demethylation of the genome after fertilization is an important step to initiate zygote gen...

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Autores principales: Ghazimoradi, Mohammad H., Hasegawa, Kouichi, Zolghadr, Ehsan, Montazeri, Samaneh, Farivar, Shirin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9859804/
https://www.ncbi.nlm.nih.gov/pubmed/36670207
http://dx.doi.org/10.1038/s41598-023-28457-8
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author Ghazimoradi, Mohammad H.
Hasegawa, Kouichi
Zolghadr, Ehsan
Montazeri, Samaneh
Farivar, Shirin
author_facet Ghazimoradi, Mohammad H.
Hasegawa, Kouichi
Zolghadr, Ehsan
Montazeri, Samaneh
Farivar, Shirin
author_sort Ghazimoradi, Mohammad H.
collection PubMed
description Many attempts have been made to induce high-quality embryonic stem cells such as pluripotent stem cells and totipotent stem cells, but challenges remain to be overcome such as appropriate methods and sources. Demethylation of the genome after fertilization is an important step to initiate zygote gene activation, which can lead to the development of new embryos. Here, we tried to induce totipotent stem cells by mimicking DNA demethylation patterns of the embryo. Our data showed, after induction of DNA demethylation via chemicals or knockdown of Dnmts, cells positive for Nanog, and Cdx2 emerged. These cells could differentiate into the pluripotent and trophoblast lineage cells in-vitro. After transferring these cells to the uterus, they can implant and form embryo-like structures. Our study showed the importance of DNA demethylation roles in totipotent stem cell induction and a new and easy way to induce this cell type.
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spelling pubmed-98598042023-01-22 Reprogramming of fibroblast cells to totipotent state by DNA demethylation Ghazimoradi, Mohammad H. Hasegawa, Kouichi Zolghadr, Ehsan Montazeri, Samaneh Farivar, Shirin Sci Rep Article Many attempts have been made to induce high-quality embryonic stem cells such as pluripotent stem cells and totipotent stem cells, but challenges remain to be overcome such as appropriate methods and sources. Demethylation of the genome after fertilization is an important step to initiate zygote gene activation, which can lead to the development of new embryos. Here, we tried to induce totipotent stem cells by mimicking DNA demethylation patterns of the embryo. Our data showed, after induction of DNA demethylation via chemicals or knockdown of Dnmts, cells positive for Nanog, and Cdx2 emerged. These cells could differentiate into the pluripotent and trophoblast lineage cells in-vitro. After transferring these cells to the uterus, they can implant and form embryo-like structures. Our study showed the importance of DNA demethylation roles in totipotent stem cell induction and a new and easy way to induce this cell type. Nature Publishing Group UK 2023-01-20 /pmc/articles/PMC9859804/ /pubmed/36670207 http://dx.doi.org/10.1038/s41598-023-28457-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ghazimoradi, Mohammad H.
Hasegawa, Kouichi
Zolghadr, Ehsan
Montazeri, Samaneh
Farivar, Shirin
Reprogramming of fibroblast cells to totipotent state by DNA demethylation
title Reprogramming of fibroblast cells to totipotent state by DNA demethylation
title_full Reprogramming of fibroblast cells to totipotent state by DNA demethylation
title_fullStr Reprogramming of fibroblast cells to totipotent state by DNA demethylation
title_full_unstemmed Reprogramming of fibroblast cells to totipotent state by DNA demethylation
title_short Reprogramming of fibroblast cells to totipotent state by DNA demethylation
title_sort reprogramming of fibroblast cells to totipotent state by dna demethylation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9859804/
https://www.ncbi.nlm.nih.gov/pubmed/36670207
http://dx.doi.org/10.1038/s41598-023-28457-8
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