UW 4-Dimensional Genomic Organization of Mammalian Embryogenesis Center

项目概要/摘要 了解4D核组的大多数努力的一个主要缺点是，他们主要集中在体外 细胞系，而不是动态的体内系统。可以说，最重要的体内系统， 恰好是最具活力的，是发展本身，其中核组既塑造，又被塑造。 无数哺乳动物细胞类型的最初出现。虽然这些体内动力学目前很差， 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 哺乳动物组织中核形态学和相关分子测量的系统数据集， 细胞类型。这些数据集将在哺乳动物的主要模式生物的背景下生成。 发展，老鼠。我们的方法集中在以下核结构，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”的组合， (VCS)这些方法都是成熟的，大部分是在我们自己的实验室里开发的。我们的目标是创造一个高- 解析4DN小鼠胚胎发生图谱为社区。不同类型的数据将被整合， 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 与哺乳动物发育相关的途径。

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.