Role of Epigenetically Active Environmental Compounds in Neurodevelopmental Disorders
Role of Epigenetically Active Environmental Compounds in Neurodevelopmental Disorders
批准号:
9979666
负责人:
ALEXEY V TERSKIKH
金额:
$29.25万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-09-25 至 2022-08-31
关键词:
3-DimensionalATAC-seqAddressAffectAntidotesAromatic Polycyclic HydrocarbonsBioinformaticsBiologicalBiological AssayBiological ProcessBrainCase StudyCell DeathCell LineCellsChIP-seqChemicalsCollectionDataData SetDecision MakingDevelopmentEnvironmentEpigenetic ProcessExposure toFetal DevelopmentFlowchartsFrequenciesFutureGenotypeGoalsGuidelinesHumanHuman DevelopmentHuman bodyIn VitroIndividualLaboratoriesLibrariesLinkMachine LearningNeuritesNeurodevelopmental DisorderNeuronal DifferentiationNeuronsPatientsPatternPhasePlant RootsProcessProtective AgentsRegulationRiskRoleServicesTechniquesTestingThalidomideToxic effectToxicity TestsToxicologyValidationValproic AcidVertebratesadverse outcomeautism spectrum disorderbasebisphenol Acell growthcost effectivecytotoxicitydashboardenvironmental chemicalepigenomeexperimental studyhigh throughput screeninghistone modificationhuman modelin vivoinduced pluripotent stem cellinsightmicroscopic imagingnerve stem cellneurodevelopmentnovelnovel strategiesphthalatesprogenitorrelating to nervous systemscreeningself-renewalsmall molecule librariesstemstem cell fatestem cell modelsynaptogenesistooltranscriptome sequencing
中文摘要
项目摘要
神经发育障碍(NDD)越来越多地被认为起源于神经发育障碍的调节异常。
早期的大脑发育,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
大规模的细胞死亡,但通过其对干细胞命运和谱系的表观遗传效应改变脑功能
发展然而,系统地研究环境对表观遗传影响的工具,
神经系统缺乏。在这里,我们采用表观遗传景观显微成像(MIEL),
筛选ToxCast III期化学文库(4700种化合物),并表征改变表观遗传的命中物
人类神经前体的景观而不诱导细胞毒性。认识到环境损害,
了解其作用机制将有助于制定旨在
避免这种损害,并在暴露不可避免时开发解毒剂和保护剂。
英文摘要
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.
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