Establishment of a developmental toxicity assay based on human iPSC reporter to detect FGF signal disruption

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  • Kanno, Seiya
    Fac Engn, Hodogaya Ward, Yokohama National University Fac Engn, Hodogaya Ward, Div Cellular & Mol Toxicol, Ctr Biol Safety & Res, National Institute of Health Sciences - Japan
  • Okubo, Yusuke
    Fac Engn, Hodogaya Ward, Div Cellular & Mol Toxicol, Ctr Biol Safety & Res, National Institute of Health Sciences
  • Kageyama, Tatsuto
    Fac Engn, Hodogaya Ward, Yokohama National University Fac Engn, Hodogaya Ward, Div Cellular & Mol Toxicol, Ctr Biol Safety & Res, Takatsu Ward, Kanagawa Inst Ind Sci & Technol KISTEC
  • Yan, Lei
    Fac Engn, Hodogaya Ward, Yokohama National University
  • Kitajima, Satoshi
    Fac Engn, Hodogaya Ward, Div Cellular & Mol Toxicol, Ctr Biol Safety & Res, National Institute of Health Sciences
  • Fukuda, Junji
    Fac Engn, Hodogaya Ward, Yokohama National University Fac Engn, Hodogaya Ward, Div Cellular & Mol Toxicol, Ctr Biol Safety & Res, Takatsu Ward, Kanagawa Inst Ind Sci & Technol KISTEC

書誌事項

公開日
2022-02-02
資源種別
journal article
権利情報
  • Creative Commons Attribution 4.0 International
DOI
  • 10.1016/j.isci.2022.103770
公開者
Cell Press

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説明

The number of man-made chemicals has increased exponentially recently, and exposure to some of them can induce fetal malformations. Because complex and precisely programmed signaling pathways play important roles in develop-mental processes, their disruption by external chemicals often triggers develop-mental toxicity. However, highly accurate and high-throughput screening assays for potential developmental toxicants are currently lacking. In this study, we pro-pose a reporter assay that utilizes human-induced pluripotent stem cells (iPSCs) to detect changes in fibroblast growth factor signaling, which is essential for limb morphogenesis. The dynamics of this signaling after exposure to a chemical were integrated to estimate the degree of signaling disruption, which afforded a good prediction of the capacity of chemicals listed in the ECVAM International Validation Study that induce limb malformations. This study presents an initial report of a human iPSC-based signaling disruption assay, which could be useful for the screening of potential developmental toxicants.

収録刊行物

  • iScience

    iScience 25 (2), 103770-, 2022-02-02

    Cell Press

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