Role of Epigenetically Active Environmental Compounds in Neurodevelopmental Disorders

项目摘要 神经发育障碍（NDD）越来越多地被认为是起源于早期神经发育障碍的失调。 大脑发育，这代表了对环境化合物的脆弱性。环境 化合物可以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发育的表观遗传效应改变脑功能。 然而，系统地研究环境对神经发育的表观遗传影响的工具是 缺乏在这里，我们采用表观遗传景观显微成像（MIEL）来筛选ToxCast e1k 化学库（1800种化合物），并表征改变人类神经系统表观遗传景观的命中 前体而不诱导细胞毒性。认识到环境的侮辱和理解他们的 行动机制将有助于制定旨在避免此类侮辱的条例和准则 以及当暴露不可避免时解毒剂和保护剂的发展。

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 e1k chemical library (1800 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.