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: 10669573
• 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/10669573
• 关键词: 3-Dimensional; ATAC-seq; Alleles; 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; Emerging Technologies; 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; 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; Stains; Statistical Methods; System; Time; Tissues; Universities; Visual; Visualization; Washington; Whole Organism; X Inactivation; cell type; data visualization; human data; human disease; imprint; in vivo; knowledge translation; lamin B receptor; machine learning model; model organism; molecular phenotype; mouse development; mouse model; mutant; novel; nucleophosmin; single-cell RNA sequencing; 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.

项目概要/摘要 大多数了解 4D 核组的努力的一个主要缺点是它们主要集中在体外 细胞系，而不是动态的体内系统，可以说是最重要的体内系统。 恰好是最具活力的，正在自我发展，但是核组既塑造形状又被塑造 多种哺乳动物细胞类型的最初出现，而这些体内动力学目前还很差。 最近出现的技术被记录和理解，提供了一条前进的道路。 华盛顿大学哺乳动物胚胎发生的 4 维基因组核组织 中心（华盛顿大学 4D 基因组中心），该中心将通过生成 关于哺乳动物组织中核形态和相关分子测量的系统数据集 这些数据集将在哺乳动物的主要模型生物的背景下生成。 我们的方法重点关注小鼠的核结构、染色质和基因表达。 使用可扩展的单细胞分析和“视觉细胞分选”相结合，在“整个有机体”规模上发生变化 (VCS) 方法，所有这些方法均已完善，并且大部分是在我们自己的实验室中开发的，我们的目标是生成高水平的方法。 社区的小鼠胚胎发生分辨率 4DN 图谱将被整合， 包括与人类数据整合的跨物种插补，以及应用的模型和导航地图 哺乳动物发育的相关途径。