Role of Epigenetically Active Environmental Compounds in Neurodevelopmental Disorders

项目总结 神经发育障碍(NDDS)，越来越多地被认为起源于 早期大脑发育，这代表了对环境化合物的脆弱性窗口。 环境化合物可能会通过表观遗传机制改变神经发育，这可能不会诱导 大量细胞死亡，但通过其对干细胞命运和谱系的表观遗传效应改变大脑功能 发展。然而，系统地研究环境对环境的表观遗传影响的工具 缺乏神经发育。在这里，我们使用表观遗传景观的显微成像(MIEL)来 筛选ToxCast第三阶段化学文库(4700个化合物)并鉴定改变表观遗传学的HITS 不会引起细胞毒性的人类神经前体景观。认识到环境的侮辱和 了解它们的行动机制将有助于制定旨在 当不可避免地暴露时，避免这种侮辱以及解毒剂和保护剂的开发。

PROJECT SUMMARY Neurodevelopmental disorders (NDDs), are increasingly recognized as originating from dysregulation of early brain development, which represents a window of vulnerability to environmental compounds. Environmental compounds may alter neurodevelopment via epigenetic mechanisms, which may not induce massive cell death, but change the brain function through their epigenetic effect on stem cell fate and lineage development. However, tools to systematically examine the epigenetic impact of environment on neurodevelopment are lacking. Here we employ Microscopic Imaging of Epigenetic Landscape (MIEL) to screen ToxCast Phase III chemical library (4700 compounds) and to characterize hits that alter epigenetic landscape of human neural precursors without inducing cytotoxicity. Recognizing environmental insults and understanding their mechanism of action will enable the development of regulations and guidelines aimed at avoiding such insults and the development of antidotes and protective agents when exposure is unavoidable.