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图谱已经从根本上 改变了分子生物学的研究方式。细胞是生命的基本单位，构成了每一个细胞 提供最准确和最精确的组织样本特征，这些组织样本可能包含许多不同的 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 基于液滴微流控技术的全基因组组蛋白修饰和传导技术 整合了表观基因组学和转录组分析的多基因组图谱。我们的单电池芯片-SEQ和MULTI- 基因组技术将允许对大量细胞进行快速检查。此外，通过大幅使用 简化的分子生物学和微流控技术，我们的scChIP-seq将产生显著的改进 基因组覆盖。我们的多基因组图谱将允许对表观基因组和转录组进行综合分析 精确理解基因调控和表达之间的特征和相关性的建立 单细胞水平上的细胞类型、命运和潜力。作为原则证明，我们将把这些技术应用于 检测迷幻药对小鼠脑生物学的影响。大脑是最复杂的器官 所涉及的细胞类型和亚群的巨大异质性和复杂性以及对 脑神经科学将从单细胞方法中受益匪浅。在这个为期4年的项目结束时， 我们将推动这些技术走向成熟，用于具有真正生物医学相关性的组织研究。

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.