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Tributyltin Inhibits Neural Induction of Human Induced Pluripotent Stem Cells

Tributyltin (TBT), one of the organotin compounds, is a well-known environmental pollutant. In our recent study, we reported that TBT induces mitochondrial dysfunction, in human-induced pluripotent stem cells (iPSCs) through the degradation of mitofusin1 (Mfn1), which is a mitochondrial fusion facto...

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Autores principales: Yamada, Shigeru, Kubo, Yusuke, Yamazaki, Daiju, Sekino, Yuko, Nomura, Yoko, Yoshida, Sachiko, Kanda, Yasunari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092327/
https://www.ncbi.nlm.nih.gov/pubmed/30108368
http://dx.doi.org/10.1038/s41598-018-30615-2
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author Yamada, Shigeru
Kubo, Yusuke
Yamazaki, Daiju
Sekino, Yuko
Nomura, Yoko
Yoshida, Sachiko
Kanda, Yasunari
author_facet Yamada, Shigeru
Kubo, Yusuke
Yamazaki, Daiju
Sekino, Yuko
Nomura, Yoko
Yoshida, Sachiko
Kanda, Yasunari
author_sort Yamada, Shigeru
collection PubMed
description Tributyltin (TBT), one of the organotin compounds, is a well-known environmental pollutant. In our recent study, we reported that TBT induces mitochondrial dysfunction, in human-induced pluripotent stem cells (iPSCs) through the degradation of mitofusin1 (Mfn1), which is a mitochondrial fusion factor. However, the effect of TBT toxicity on the developmental process of iPSCs was not clear. The present study examined the effect of TBT on the differentiation of iPSCs into the ectodermal, mesodermal, and endodermal germ layers. We found that exposure to nanomolar concentration of TBT (50 nM) selectively inhibited the induction of iPSCs into the ectoderm, which is the first step in neurogenesis. We further assessed the effect of TBT on neural differentiation and found that it reduced the expression of several neural differentiation marker genes, which were also downregulated by Mfn1 knockdown in iPSCs. Taken together, these results indicate that TBT induces developmental neurotoxicity via Mfn1-mediated mitochondrial dysfunction in iPSCs.
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spelling pubmed-60923272018-08-20 Tributyltin Inhibits Neural Induction of Human Induced Pluripotent Stem Cells Yamada, Shigeru Kubo, Yusuke Yamazaki, Daiju Sekino, Yuko Nomura, Yoko Yoshida, Sachiko Kanda, Yasunari Sci Rep Article Tributyltin (TBT), one of the organotin compounds, is a well-known environmental pollutant. In our recent study, we reported that TBT induces mitochondrial dysfunction, in human-induced pluripotent stem cells (iPSCs) through the degradation of mitofusin1 (Mfn1), which is a mitochondrial fusion factor. However, the effect of TBT toxicity on the developmental process of iPSCs was not clear. The present study examined the effect of TBT on the differentiation of iPSCs into the ectodermal, mesodermal, and endodermal germ layers. We found that exposure to nanomolar concentration of TBT (50 nM) selectively inhibited the induction of iPSCs into the ectoderm, which is the first step in neurogenesis. We further assessed the effect of TBT on neural differentiation and found that it reduced the expression of several neural differentiation marker genes, which were also downregulated by Mfn1 knockdown in iPSCs. Taken together, these results indicate that TBT induces developmental neurotoxicity via Mfn1-mediated mitochondrial dysfunction in iPSCs. Nature Publishing Group UK 2018-08-14 /pmc/articles/PMC6092327/ /pubmed/30108368 http://dx.doi.org/10.1038/s41598-018-30615-2 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
Yamada, Shigeru
Kubo, Yusuke
Yamazaki, Daiju
Sekino, Yuko
Nomura, Yoko
Yoshida, Sachiko
Kanda, Yasunari
Tributyltin Inhibits Neural Induction of Human Induced Pluripotent Stem Cells
title Tributyltin Inhibits Neural Induction of Human Induced Pluripotent Stem Cells
title_full Tributyltin Inhibits Neural Induction of Human Induced Pluripotent Stem Cells
title_fullStr Tributyltin Inhibits Neural Induction of Human Induced Pluripotent Stem Cells
title_full_unstemmed Tributyltin Inhibits Neural Induction of Human Induced Pluripotent Stem Cells
title_short Tributyltin Inhibits Neural Induction of Human Induced Pluripotent Stem Cells
title_sort tributyltin inhibits neural induction of human induced pluripotent stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092327/
https://www.ncbi.nlm.nih.gov/pubmed/30108368
http://dx.doi.org/10.1038/s41598-018-30615-2
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