Comprehensive analysis of chromatin architecture is crucial for understanding the gene regulatory programs during development and in disease pathogenesis, yet current methods often inadequately address the unique challenges presented by analysis of heterogeneous tissue samples. Here, we introduce Droplet Hi-C, which employs a commercial microfluidic device for high-throughput, single-cell chromatin conformation profiling in droplets. Using Droplet Hi-C, we mapped the chromatin architecture at single-cell resolution from the mouse cortex and analyzed gene regulatory programs in major cortical cell types. Additionally, we used this technique to detect copy number variation (CNV), structural variations (SVs) and extrachromosomal DNA (ecDNA) in cancer cells, revealing clonal dynamics and other oncogenic events during treatment. We further refined this technique to allow for joint profiling of chromatin architecture and transcriptome in single cells, facilitating a more comprehensive exploration of the links between chromatin architecture and gene expression in both normal tissues and tumors. Thus, Droplet Hi-C not only addresses critical gaps in chromatin analysis of heterogeneous tissues but also emerges as a versatile tool enhancing our understanding of gene regulation in health and disease.

中文翻译：

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Droplet Hi-C 用于单细胞染色质结构的快速且可扩展的分析

染色质结构的综合分析对于理解发育过程和疾病发病机制中的基因调控程序至关重要，但目前的方法往往不足以解决异质组织样本分析所带来的独特挑战。在这里，我们介绍 Droplet Hi-C，它采用商业微流体装置来进行液滴中的高通量、单细胞染色质构象分析。使用 Droplet Hi-C，我们以单细胞分辨率绘制了小鼠皮质的染色质结构图，并分析了主要皮质细胞类型的基因调控程序。此外，我们使用该技术检测癌细胞中的拷贝数变异 (CNV)、结构变异 (SV) 和染色体外 DNA (ecDNA)，揭示治疗期间的克隆动态和其他致癌事件。我们进一步完善了这项技术，以允许对单细胞中的染色质结构和转录组进行联合分析，从而促进更全面地探索正常组织和肿瘤中染色质结构与基因表达之间的联系。因此，Droplet Hi-C 不仅解决了异质组织染色质分析中的关键空白，而且还成为增强我们对健康和疾病基因调控的理解的多功能工具。