Droplet microfluidic technology for single-cell epigenomic and multi-omic profiling

用于单细胞表观基因组和多组学分析的液滴微流体技术

基本信息

批准号：
10491742
负责人：
Chang Lu
金额：
$ 32.42万
依托单位：
VIRGINIA POLYTECHNIC INST AND ST UNIV
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10491742
关键词：
Address Affect Antidepressive Agents Biology Brain Cells ChIP-seq Characteristics Chemistry Chromatin Complex DNA Sequence Data Data Set Development Disease Epigenetic Process Exhibits Gene Expression Gene Expression Regulation Genes Genome Genome Mappings Genomics Gold Hallucinogens Heterogeneity Individual Injections Life Measurement Microfluidic Microchips Microfluidics Molecular Biology Molecular Conformation Multiomic Data Mus Neurons Neurosciences Organ Phenotype Play Process Protocols documentation Role Technology Tissue Sample Tissues Work base brain cell cell type chromatin immunoprecipitation cost design drug discovery epigenome epigenomics frontal lobe genome-wide genome-wide analysis histone modification improved insight microfluidic technology multiple omics next generation sequencing precision medicine response screening single cell analysis single cell technology single-cell RNA sequencing tool trait transcriptome transcriptome sequencing transcriptomics whole genome

项目摘要

Project Summary Single-cell genome-wide profiling enabled by next-generation sequencing (NGS) has been fundamentally changing how molecular biology is studied. Cells are basic unit of life and profiling each individual cell provides the most accurate and precise characterization of tissue samples that likely contain numerous diverse cell types and subpopulations. In this project, we will develop high-throughput and high-quality single-cell technologies based on droplet microfluidics for mapping genome-wide histone modifications and conducting multi-omic profiling that integrates epigenomic and transcriptomic analyses. Our single-cell ChIP-seq and multi- omic technology will allow massive number of cells to be examined rapidly. Furthermore, by using drastically simplified molecular biology and microfluidic technology, our scChIP-seq will produce significantly improved genome coverage. Our multi-omic profiling will allow integrative analysis of epigenomic and transcriptomic features and establishment of correlations between gene regulation and expression for precise understanding of cell type, fate and potential at the single cell level. As a proof-of-principle, we will apply these technologies to examine the effects of psychedelic drug on mouse brain biology. Brain is the most complex organ that exhibit enormous heterogeneity and complexity in terms of the cell types and subpopulations involved and studies of brain neuroscience will benefit from the single-cell approach tremendously. By the end of this 4-year project, we will push these technologies to maturity for tissue-based studies with real biomedical relevance.

项目摘要下一代测序（NGS）启用了单细胞全基因组分析。改变研究分子生物学的研究。细胞是生命的基本单位，并分析每个单独的单元提供可能包含大量多样性的组织样品的最准确和精确的表征细胞类型和亚群。在这个项目中，我们将开发高通量和高质量的单细胞基于液滴微流体的技术，用于绘制全基因组组蛋白的修饰和进行整合表观基因组和转录组分析的多矩分析。我们的单细胞芯片序列和多 OMIC技术将允许大量细胞进行迅速检查。此外，通过大量使用简化的分子生物学和微流体技术，我们的SCchip-Seq将产生显着改善基因组覆盖范围。我们的多词分析将允许对表观基因组和转录组的整合分析基因调节和表达之间的特征和建立相关性，以精确理解单细胞水平的细胞类型，命运和潜力。作为原理证明，我们将把这些技术应用于检查迷幻药对小鼠脑生物学的影响。大脑是表现最复杂的器官关于细胞类型和涉及的细胞类型和亚群的巨大异质性和复杂性以及研究大脑神经科学将大大受益于单细胞方法。到这个4年项目结束时，我们将把这些技术推向具有实际生物医学相关性的基于组织的研究的成熟度。