UW 4-Dimensional Genomic Organization of Mammalian Embryogenesis Center

威斯康星大学哺乳动物胚胎发生中心 4 维基因组组织

• 批准号: 10265565
• 负责人: Christine M. Disteche
• 金额: $ 203.11万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-18 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10265565
• 关键词: 3-Dimensional; ATAC-seq; Address; Alleles; Animal Model; Antibodies; Architecture; Atlases; Biological Assay; C57BL/6 Mouse; Cell Line; Cell Nucleolus; Cell Nucleus; Cell Separation; Cells; Chromatin; Chromatin Structure; Chromosomes; Communities; DNA; Data; Data Collection; Data Set; Development; Disease; Embryo; Embryonic Development; Four-dimensional; Gene Expression; Gene Mutation; Generations; Genes; Genetic Transcription; Genome; Genomics; Goals; Heterochromatin; Hi-C; Hour; Human; Hybrids; Image; In Vitro; Lamin Type A; Machine Learning; Malignant Neoplasms; Mammalian Cell; Maps; Measurement; Methods; Modeling; Molecular; Molecular Conformation; Molecular Profiling; Morphology; Mus; Mutation; Nuclear; Nuclear Structure; Pathway interactions; Phenotype; Positioning Attribute; RNA; Resolution; Series; Shapes; Sorting - Cell Movement; Stains; Statistical Methods; System; Technology; Time; Tissues; Universities; Visual; Visualization; Washington; Whole Organism; X Inactivation; base; cell type; human data; human disease; imprint; in vivo; knowledge translation; lamin B receptor; molecular phenotype; mouse development; mouse model; mutant; novel; nucleophosmin; transcriptome sequencing; web portal

Project Summary / Abstract A major shortcoming of most efforts to understand the 4D nucleome is that they have mainly focused on in vitro cell lines, rather than on dynamic, in vivo systems. Arguably, the most important in vivo system, which also happens to be the most dynamic, is development itself, wherein the nucleome both shapes and is shaped by the initial emergence of the myriad mammalian cell types. While these in vivo dynamics are presently poorly documented and understood, recently emerged technologies offer a path forward. Here we propose to establish the University of Washington 4-Dimensional Genomic Nuclear Organization of Mammalian Embryogenesis Center (UW 4D GENOME Center), which will address these massive gaps in our understanding by generating systematic datasets on nuclear morphology and associated molecular measurements in mammalian tissues and cell types. These datasets will be generated in the context of the leading model organism for mammalian development, the mouse. Our approach focuses on following nuclear structure, chromatin and gene expression changes at a “whole organism” scale, using a combination of scalable single cell profiling and “visual cell sorting” (VCS) methods, all well-established and mostly developed in our own labs. Our goal is to generate a high- resolution 4DN atlas of mouse embryogenesis for the community. The different types of data will be integrated, including cross-species imputation to integrate with human data, as well as models and navigable maps applied to pathways relevant to mammalian development.

项目摘要/摘要 大多数了解4D基因组的努力的一个主要缺点是，他们主要集中在体外 细胞系，而不是动态的活体系统。可以说，体内最重要的系统，也 恰好是最具活力的，是发育本身，其中核仁既塑造了形状，也被塑造了 最初出现了无数种哺乳动物细胞类型。虽然这些体内动力学目前还很差 经过记录和理解，最近出现的技术提供了一条前进的道路。在这里，我们建议建立 华盛顿大学哺乳动物胚胎发生的四维基因组核组织 中心(UW 4D基因组中心)，它将通过生成 哺乳动物组织和组织中核形态和相关分子测量的系统数据集 单元类型。这些数据集将在领先的哺乳动物模式生物的背景下生成 发展，鼠标。我们的方法关注于核结构、染色质和基因表达 使用可伸缩的单细胞图谱和“视觉细胞分类”的组合，在“整个有机体”的尺度上进行变化 (风险投资)方法，都是成熟的，大多是在我们自己的实验室开发的。我们的目标是创造一个高- 4DN社群小鼠胚胎发育图谱解析。不同类型的数据将被集成， 包括跨物种归因以与人类数据相结合，以及应用的模型和导航地图 到与哺乳动物发育相关的途径。