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Role of Epigenetically Active Environmental Compounds in Neurodevelopmental Disorders

表观遗传活性环境化合物在神经发育障碍中的作用

基本信息

批准号：
10271253
负责人：
ALEXEY V TERSKIKH
金额：
$ 24.38万
依托单位：
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-25 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10271253
关键词：
3-Dimensional ASD patient ATAC-seq Address Affect Antidotes Aromatic Polycyclic Hydrocarbons Bioinformatics Biological Biological Assay Biological Process Brain Case Study Cell Death Cell Line Cells ChIP-seq Chemicals Collection Data Data Set Decision Making Development Environment Epigenetic Process Exposure to Fetal Development Flowcharts Frequencies Future Genotype Goals Guidelines Human Human Development Human body In Vitro Individual Laboratories Libraries Link Machine Learning Neurites Neurodevelopmental Disorder Neuronal Differentiation Neurons Patients Pattern Phase Plant Roots Process Protective Agents Regulation Risk Role Services Techniques Testing Thalidomide Toxic effect Toxicity Tests Toxicology Validation Valproic Acid Vertebrates adverse outcome autism spectrum disorder base bisphenol A cell growth cost effective cytotoxicity dashboard environmental chemical epigenome experimental study high throughput screening histone modification human model in vivo induced pluripotent stem cell insight microscopic imaging nerve stem cell neurodevelopment novel novel strategies phthalates progenitor relating to nervous system screening self-renewal small molecule libraries stem stem cell fate stem cell model synaptogenesis tool transcriptome sequencing

项目摘要

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.

项目概要神经发育障碍（NDD）越来越多地被认为是由神经发育失调引起的早期大脑发育，代表着对环境化合物的脆弱性的一个窗口。环境化合物可能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，系统地检查环境对表观遗传影响的工具神经发育缺乏。在这里，我们采用表观遗传景观显微成像 (MIEL) 来筛选 ToxCast 第三阶段化学库（4700 种化合物）并表征改变表观遗传的命中人类神经前体的景观而不诱导细胞毒性。认识到环境侮辱和了解其作用机制将有助于制定旨在避免此类侮辱，并在暴露不可避免时开发解毒剂和保护剂。