Modeling Histone Demethylase Function in Neurogenesis

模拟神经发生中的组蛋白去甲基化酶功能

• 批准号: 10527660
• 负责人: ANITA BHATTACHARYYA
• 金额: $ 41.43万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10527660
• 关键词: Affect; Ascorbic Acid; Autopsy; Biological Models; Brain; Brain Diseases; Cell Fate Control; Cell physiology; Cells; Cerebral cortex; Code; Complex; DNA; Data; Defect; Development; Disease; Enzymes; Epigenetic Process; Etiology; Family; Foundations; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Gene Mutation; Genes; Genetic Transcription; Genomics; Grant; Heterogeneity; Histones; Human; Individual; Intellectual functioning disability; Lead; Link; Location; Lysine; Methyl-CpG-Binding Protein 2; Methylation; Modeling; Modification; Molecular; Mutation; Neurodevelopmental Deficit; Neurodevelopmental Disorder; Neuronal Differentiation; Neurons; Pathogenesis; Pathogenicity; Pathway interactions; Phenotype; Play; Proteins; Rare Diseases; Reader; Resources; Rett Syndrome; Role; Severities; Testing; Variant; alpha ketoglutarate; autism spectrum disorder; chromatin remodeling; cognitive function; epigenome; experimental study; gene environment interaction; gene function; genome-wide; genome-wide analysis; histone demethylase; human embryonic stem cell; human pluripotent stem cell; human stem cells; induced pluripotent stem cell; loss of function; mutant; negative affect; nerve stem cell; nervous system disorder; neurodevelopment; neurogenesis; neuron development; transcriptome; transcriptome sequencing

ABSTRACT Cortical development is dependent on the coordinated expression of critical genes for proper cognitive function. Alterations in expression of these key genes during development can result in complex neurological diseases. Epigenetic mechanisms dynamically regulate expression of key genes and their loss of function disrupts cortical development and contributes to brain disorders. Rare pathogenic mutations in one epigenetic factor, KDM3B, are linked to intellectual disability and autism spectrum disorders (ASD). This exploratory proposal will test the functional consequences of these KDM3B mutations on cortical development using human embryonic stem cells with mutations of KDM3B. We will investigate both cellular and molecular differences between mutant and control cells as they differentiate into neural progenitor cells and neurons. Integration of these cellular data with molecular data will reveal the direct effects of intellectual disability related mutations in KDM3B to neurodevelopment.

摘要

项目成果

Anterior thalamic circuits crucial for working memory.

• DOI: 10.1073/pnas.2118712119
• 发表时间: 2022-05-17
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1