Integrated Epigenetic Maps of Human Embryonic and Adult Cells

人类胚胎和成体细胞的综合表观遗传图谱

• 批准号: 8143949
• 负责人: Joseph F Costello
• 金额: $ 41.85万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8143949
• 关键词: Address; Adult; Alleles; Base Sequence; Biological; Blood; Blood Cells; Brain; Brain Stem; Breast; British Columbia; California; Cell Count; Cell Cycle; Cells; Centromere; Chromatin; Chromosomes; Communities; Complex; DNA Methylation; Data; Data Analyses; Data Coordinating Center; Discipline; Disease; Disease susceptibility; Embryo; Enhancers; Environment; Enzymes; Epigenetic Process; Evolution; Female; Funding; Future; Gender; Gene Expression; Gene Expression Profile; Genes; Genetic; Genome; Goals; Government; Health; Histones; Human; Immunoprecipitation; Informatics; Knowledge; Laboratories; Leukocytes; Libraries; Maintenance; Maps; Methods; Methylation; MicroRNAs; Modeling; Molecular Profiling; Nucleic Acid Regulatory Sequences; Physiological; Population; Preparation; Principal Investigator; Process; Production; Protocols documentation; Qualifying; RNA; Race; Reading; Reference Values; Regulation; Repetitive Sequence; Research; Research Personnel; Resolution; Resources; Role; Sampling; Science; Scientist; Sequence Analysis; Shotgun Sequencing; Site; Small RNA; Software Tools; Specimen; Stem cells; Structure; Technology; Therapeutic; Tissues; United States National Institutes of Health; Universities; Validation; Work; base; cell type; chromatin immunoprecipitation; chromatin modification; comparative; cost; data sharing; embryonic stem cell; epigenomics; experience; histone modification; human disease; human embryonic stem cell line; imprint; instrument; male; next generation; programs; promoter; public health relevance; research study; restriction enzyme; telomere; tissue regeneration; tool

DESCRIPTION (provided by applicant): We propose to work cooperatively with other Mapping Centers and the Data Coordination Center (EDACC) funded by this Roadmap mechanism to comprehensively map epigenomes of select human cells with significant relevance to complex human disease. Our group, consisting of scientists at UCSF, UC Davis, UCSC and the British Columbia Genome Sciences Centre has the broad expertise that this project requires. We will focus on cells relevant to human health and complex disease including cells from the blood, brain, breast and U.S. Government-approved lines of human embryonic stem cells (aim 1). We will incorporate high quality, homogeneous cells from males and females, and two predominant racial groups, and biological replicates of each cell type. Production of comprehensive maps will include 6 histone modifications selected for their opposing roles in regulating active and inactive chromatin (aim 2), DNA methylation (aim 3) and miRNA and gene expression (aim 4). This epigenetic data, along with genetic and expression data will be integrated using advanced informatics (aim 5) to address fundamental roles of epigenetics in differentiation, maintenance of cell-type identity and gene expression. Our cell and data production pipeline will incorporate verification and data validation with independent methods, and will operate under a model motivated by increased data production and decrease cost. We summarize the analysis capacity of our instruments and our explicit strategy for data sharing of our proposed REMC-generated resources including biological specimens, protocols, data, software tools and intellectual resources. We envision that our group in conjunction with the other REMC teams, the EDACC, ENCODE, future EHHD (Epigenetics of Human Health and Disease) centers and the NIH Roadmap program will develop methods, tools and reference epigenome maps for the research community that will make the promise of epigenetics in understand and treating human complex disease a reality. Our reference epigenomes will enable new disciplines including human population epigenetics, comparative epigenomics, neuroepigenetics, and therapeutic epigenetics for tissue regeneration and reversal of disease. PUBLIC HEALTH RELEVANCE: The epigenome is the dynamic interface between our changing environment and the static genome, and understanding it is a goal of immense importance to human health. We will map reference cell epigenomes of the brain, breast, blood and approved embryonic stem cells, inclusive of males and females and different racial groups. This cooperative work will transform our understanding of the short and long-lasting consequences of environment impact on human health and disease.

描述（由申请人提供）：我们建议与该路线图机制资助的其他绘图中心和数据协调中心（EDACC）合作，全面绘制与复杂人类疾病显着相关的选定人类细胞的表观基因组图谱。我们的团队由加州大学旧金山分校、加州大学戴维斯分校、加州大学圣地亚哥分校和不列颠哥伦比亚省基因组科学中心的科学家组成，拥有该项目所需的广泛专业知识。我们将重点关注与人类健康和复杂疾病相关的细胞，包括来自血液、大脑、乳腺的细胞和美国政府批准的人类胚胎干细胞系（目标 1）。我们将整合来自男性和女性以及两个主要种族群体的高质量、同质细胞，以及每种细胞类型的生物复制品。综合图谱的制作将包括 6 个组蛋白修饰，这些修饰因其在调节活性和非活性染色质（目标 2）、DNA 甲基化（目标 3）以及 miRNA 和基因表达（目标 4）方面的相反作用而被选择。这些表观遗传学数据以及遗传和表达数据将使用先进的信息学（目标 5）进行整合，以解决表观遗传学在分化、细胞类型身份维持和基因表达中的基本作用。我们的细胞和数据生产管道将采用独立方法整合验证和数据验证，并将在增加数据生产和降低成本的模型下运行。我们总结了我们仪器的分析能力以及我们提出的 REMC 生成资源（包括生物标本、方案、数据、软件工具和智力资源）的数据共享的明确策略。我们设想，我们的团队与其他 REMC 团队、EDACC、ENCODE、未来的 EHHD（人类健康和疾病表观遗传学）中心和 NIH 路线图计划一起，将为研究界开发方法、工具和参考表观基因组图谱，使表观遗传学在理解和治疗人类复杂疾病方面的承诺成为现实。我们的参考表观基因组将使新学科成为可能，包括人类表观遗传学、比较表观基因组学、神经表观遗传学以及组织再生和疾病逆转的治疗表观遗传学。公共卫生相关性：表观基因组是我们不断变化的环境和静态基因组之间的动态界面，了解它是对人类健康极其重要的目标。我们将绘制大脑、乳房、血液和批准的胚胎干细胞的参考细胞表观基因组图谱，包括男性和女性以及不同种族群体。这项合作将改变我们对环境影响对人类健康和疾病的短期和长期后果的理解。