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A method for human teratogen detection by geometrically confined cell differentiation and migration
Unintended exposure to teratogenic compounds can lead to various birth defects; however current animal-based testing is limited by time, cost and high inter-species variability. Here, we developed a human-relevant in vitro model, which recapitulated two cellular events characteristic of embryogenesi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428054/ https://www.ncbi.nlm.nih.gov/pubmed/25966467 http://dx.doi.org/10.1038/srep10038 |
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author | Xing, Jiangwa Toh, Yi-Chin Xu, Shuoyu Yu, Hanry |
author_facet | Xing, Jiangwa Toh, Yi-Chin Xu, Shuoyu Yu, Hanry |
author_sort | Xing, Jiangwa |
collection | PubMed |
description | Unintended exposure to teratogenic compounds can lead to various birth defects; however current animal-based testing is limited by time, cost and high inter-species variability. Here, we developed a human-relevant in vitro model, which recapitulated two cellular events characteristic of embryogenesis, to identify potentially teratogenic compounds. We spatially directed mesoendoderm differentiation, epithelial-mesenchymal transition and the ensuing cell migration in micropatterned human pluripotent stem cell (hPSC) colonies to collectively form an annular mesoendoderm pattern. Teratogens could disrupt the two cellular processes to alter the morphology of the mesoendoderm pattern. Image processing and statistical algorithms were developed to quantify and classify the compounds’ teratogenic potential. We not only could measure dose-dependent effects but also correctly classify species-specific drug (Thalidomide) and false negative drug (D-penicillamine) in the conventional mouse embryonic stem cell test. This model offers a scalable screening platform to mitigate the risks of teratogen exposures in human. |
format | Online Article Text |
id | pubmed-4428054 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44280542015-05-21 A method for human teratogen detection by geometrically confined cell differentiation and migration Xing, Jiangwa Toh, Yi-Chin Xu, Shuoyu Yu, Hanry Sci Rep Article Unintended exposure to teratogenic compounds can lead to various birth defects; however current animal-based testing is limited by time, cost and high inter-species variability. Here, we developed a human-relevant in vitro model, which recapitulated two cellular events characteristic of embryogenesis, to identify potentially teratogenic compounds. We spatially directed mesoendoderm differentiation, epithelial-mesenchymal transition and the ensuing cell migration in micropatterned human pluripotent stem cell (hPSC) colonies to collectively form an annular mesoendoderm pattern. Teratogens could disrupt the two cellular processes to alter the morphology of the mesoendoderm pattern. Image processing and statistical algorithms were developed to quantify and classify the compounds’ teratogenic potential. We not only could measure dose-dependent effects but also correctly classify species-specific drug (Thalidomide) and false negative drug (D-penicillamine) in the conventional mouse embryonic stem cell test. This model offers a scalable screening platform to mitigate the risks of teratogen exposures in human. Nature Publishing Group 2015-05-12 /pmc/articles/PMC4428054/ /pubmed/25966467 http://dx.doi.org/10.1038/srep10038 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Xing, Jiangwa Toh, Yi-Chin Xu, Shuoyu Yu, Hanry A method for human teratogen detection by geometrically confined cell differentiation and migration |
title | A method for human teratogen detection by geometrically confined cell differentiation and migration |
title_full | A method for human teratogen detection by geometrically confined cell differentiation and migration |
title_fullStr | A method for human teratogen detection by geometrically confined cell differentiation and migration |
title_full_unstemmed | A method for human teratogen detection by geometrically confined cell differentiation and migration |
title_short | A method for human teratogen detection by geometrically confined cell differentiation and migration |
title_sort | method for human teratogen detection by geometrically confined cell differentiation and migration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428054/ https://www.ncbi.nlm.nih.gov/pubmed/25966467 http://dx.doi.org/10.1038/srep10038 |
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