Integrative single-cell spatial genomic, transcriptomic, and epigenetic imaging in mammalian tissue

哺乳动物组织中的综合单细胞空间基因组、转录组和表观遗传成像

基本信息

批准号：
10631166
负责人：
Siyuan Wang
金额：
$ 51.58万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-10 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10631166
关键词：
3-Dimensional Address Adult Affect Aging Architecture Biological Assay Biological Process Biomedical Research Cell Culture Techniques Cell Nucleolus Cell Nucleus Cell physiology Cells Chromatin Chromatin Loop Chromosome Territory Chromosomes Communities Complex Computer software DNA DNA-Binding Proteins Data Development Disease Enhancers Epigenetic Process Fluorescent in Situ Hybridization Future Gene Expression Gene Expression Profile Gene Expression Regulation Genetic Transcription Genome Genomic DNA Genomic Segment Genomics Health Hi-C Human Development Human body Image Imaging technology In Situ In Vitro Length Malignant Neoplasms Mammalian Cell Maps Measurement Measures Methodology Methods Mus Nuclear Nuclear Lamina Pattern Process Progeria RNA Research Research Personnel Resolution Structure Techniques Technology Testing Three-dimensional analysis Time Tissues Visualization Work cell behavior cell type combinatorial design epigenome experience experimental study fetal genome-wide genomic locus improved invention multiplexed imaging novel novel strategies promoter protein distribution single molecule transcriptomics user friendly software virtual

项目摘要

Project Summary/Abstract The three-dimensional (3D) organization of the genome affects many genomic functions. Multiple 3D genome architectures at different length scales, including chromatin loops, domains, compartments, and regions associated with nuclear lamina and nucleoli, have been discovered. Changes in these architectures have been associated with normal development, aging, and a wide range of diseases. However, how these structures are arranged in the same cell, how they vary in different cell types in mammalian tissue, and how they are correlated with gene expression and the epigenome in the tissue contexts are largely unknown. Current approaches are severely limited by a lack of capacity to simultaneously trace chromatin folding across multiple length scales, measure genomic organization in relation to other nuclear components, and profile gene expression and epigenome in the same single cells in mammalian tissue. To address this need, here we propose to develop a new methodology, termed Multiplexed Imaging of Nucleome Architectures (MINA), which will enable simultaneous measurements of multiscale chromatin folding, associations of genomic regions with nuclear lamina, nucleoli and other nuclear/epigenetic components, and copy numbers of numerous RNA species in the same, single cells in mammalian tissue. We expect this development to broadly impact many lines of research on 3D genomics by depicting cell-type-specific multiscale genomic architectures associated with gene expression and epigenome, in different types of tissue undergoing different biological processes. Furthermore, by allowing measurements within the same cell, it will in future be possible to directly test the causal relationship between genomic architecture and gene expression, thus opening up a completely new experimental paradigm to identify novel mechanisms that regulate gene expression across human development, health and disease.

项目摘要/摘要基因组的三维（3D）组织会影响许多基因组功能。多个3D基因组不同长度尺度的体系结构，包括染色质环，域，隔室和区域已经发现与核薄片和核仁有关。这些体系结构的变化已经与正常发育，衰老和多种疾病有关。但是，这些结构如何排列在同一细胞中，它们在哺乳动物组织中的不同细胞类型中的变化以及它们的方式与基因表达和组织环境中的表观基因组相关。当前的由于缺乏同时追踪染色质折叠的能力，方法受到严重限制长度尺度，与其他核成分相关的基因组组织，并谱图基因哺乳动物组织中同一单个细胞中的表达和表观基因组。为了满足这一需求，我们在这里提议开发一种新方法，称为核心体系结构（Mina）的多路复用成像，该成像将同时测量多尺度染色质折叠，基因组区域的关联核薄片，核仁和其他核/表观遗传组件以及众多RNA的副本数量在同一物种中，哺乳动物组织中的单细胞。我们希望这一发展将广泛影响许多通过描述细胞型特异性多尺度架构相关的细胞型基因组学研究线具有基因表达和表观基因组，在不同类型的组织中经历了不同的生物学过程。此外，通过允许在同一单元格内进行测量，将来将有可能直接测试基因组结构与基因表达之间的因果关系，从而打开了一个全新的实验范式鉴定调节人类基因表达的新机制发展，健康和疾病。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Chromatin Tracing: Imaging 3D Genome and Nucleome.

DOI：
10.1016/j.tcb.2020.10.006
发表时间：
2021-01
期刊：
Trends in cell biology
影响因子：
19
作者：
Hu M;Wang S
通讯作者：
Wang S

Female naïve human pluripotent stem cells carry X chromosomes with Xa-like and Xi-like folding conformations.

DOI：
10.1126/sciadv.adf2245
发表时间：
2023-08-04
期刊：
SCIENCE ADVANCES
影响因子：
13.6
作者：
Patterson, Benjamin;Yang, Bing;Tanaka, Yoshiaki;Kim, Kun-Yong;Cakir, Bilal;Xiang, Yangfei;Kim, Jonghun;Wang, Siyuan;Park, In-Hyun
通讯作者：
Park, In-Hyun

New mechanism of chromatin compartmentalization by BRD2.

BRD2 染色质区室化的新机制。