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

• 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
• 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

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.

项目总结