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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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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. |
format | Online Article Text |
id | pubmed-6092327 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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