液滴HI-C可以使异质组织中染色质结构的可扩展单细胞分析
Droplet Hi-C enables scalable, single-cell profiling of chromatin architecture in heterogeneous tissues
影响因子:41.70000
分区:生物学1区 Top / 生物工程与应用微生物1区
发表日期:2024 Oct 18
作者:
Lei Chang, Yang Xie, Brett Taylor, Zhaoning Wang, Jiachen Sun, Ethan J Armand, Shreya Mishra, Jie Xu, Melodi Tastemel, Audrey Lie, Zane A Gibbs, Hannah S Indralingam, Tuyet M Tan, Rafael Bejar, Clark C Chen, Frank B Furnari, Ming Hu, Bing Ren
摘要
当前用于分析染色质结构的方法不容易扩展到异质组织。在这里，我们介绍了液滴HI-C，该液滴使用商业微流体设备，用于在液滴中进行高通量，单细胞染色质构象谱。使用液滴HI-C，我们绘制了小鼠皮质的染色质结构，并分析了主要皮质细胞类型中的基因调节程序。此外，我们使用该技术来检测人胶质母细胞瘤，结直肠癌和血液癌细胞中的拷贝数变化，结构变化和外染色体DNA，揭示了治疗过程中克隆动力学和其他致癌事件。我们完善了允许单个细胞中染色质结构和转录组联合分析的技术，从而促进了染色质结构与正常组织和肿瘤中基因表达之间的联系。因此，液滴hi-c都解决了异质组织染色质分析中的关键差距，并增强了对基因调节的理解。
Abstract
Current methods for analyzing chromatin architecture are not readily scalable to heterogeneous tissues. Here we introduce Droplet Hi-C, which uses a commercial microfluidic device for high-throughput, single-cell chromatin conformation profiling in droplets. Using Droplet Hi-C, we mapped the chromatin architecture of the mouse cortex and analyzed gene regulatory programs in major cortical cell types. In addition, we used this technique to detect copy number variations, structural variations and extrachromosomal DNA in human glioblastoma, colorectal and blood cancer cells, revealing clonal dynamics and other oncogenic events during treatment. We refined the technique to allow joint profiling of chromatin architecture and transcriptome in single cells, facilitating exploration of the links between chromatin architecture and gene expression in both normal tissues and tumors. Thus, Droplet Hi-C both addresses critical gaps in chromatin analysis of heterogeneous tissues and enhances understanding of gene regulation.