Integrated Epigenetic Maps of Human Embryonic and Adult Cells

描述（由申请人提供）：我们建议与其他制图中心和由该路线图机制资助的数据协调中心（EDACC）合作，全面绘制与复杂人类疾病有重要相关性的选定人类细胞的表观基因组。我们的团队由来自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，他们拥有这个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、乳房和美国政府批准的人类胚胎干细胞系的细胞（目标1）。我们将纳入来自男性和女性以及两个优势种族的高质量、同质细胞，并对每种细胞类型进行生物复制。综合图谱的制作将包括6个组蛋白修饰，因为它们在调节活性和非活性染色质（目标2）、DNA甲基化（目标3）和miRNA和基因表达（目标4）方面具有相反的作用。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、维持细胞类型身份和基因表达中的基本作用。我们的细胞和数据生产管道将结合独立方法的验证和数据验证，并将在增加数据生产和降低成本的模型下运行。我们总结了我们的仪器的分析能力和我们提出的remc生成资源的数据共享的明确策略，包括生物标本、协议、数据、软件工具和智力资源。我们设想，我们的团队将与其他REMC团队、EDACC、ENCODE、未来的EHHD（人类健康与疾病表观遗传学）中心和NIH路线图计划合作，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促成新的学科，包括人类群体表观遗传学、比较表观基因组学、神经表观遗传学和用于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接口，了解它对人类健康具有极其重要的意义。我们将绘制脑、乳腺、血液和经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。这项合作工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。

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.