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

项目摘要 由下一代测序（NGS）实现的单细胞全基因组分析已经从根本上 改变了分子生物学的研究方式细胞是生命的基本单位， 提供了组织样本的最准确和精确的表征， 细胞类型和亚群。在本项目中，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的组蛋白修饰， 整合表观基因组学和转录组学分析的多组学分析。我们的单细胞ChIP-seq和多- 组学技术将允许快速检查大量细胞。此外，通过大量使用 简化的分子生物学和微流控技术，我们的scChIP-seq将产生显着改善 基因组覆盖率我们的多组学分析将允许对表观基因组和转录组进行整合分析。 特征和建立基因调控与表达之间的相关性，以便准确理解 细胞类型、命运和潜力的研究。作为一个原理证明，我们将把这些技术应用于 研究迷幻药对小鼠大脑生物学的影响。大脑是人体内最复杂的器官， 在涉及的细胞类型和亚群方面存在巨大的异质性和复杂性， 脑神经科学将从单细胞方法中受益匪浅。在这个为期四年的项目结束时， 我们将把这些技术推向成熟，用于具有真实的生物医学相关性的基于组织的研究。

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.