High-throughput combinatorial indexing enables scalable single-cell chromatin accessibility profiling [Blood]. High-throughput combinatorial indexing enables scalable single-cell chromatin accessibility profiling [Blood]

While recent technical advancements have facilitated the mapping of epigenomes at the single-cell resolution, the throughput and quality of these methods have limited the widespread application of these technologies. Here, we describe a high-throughput platform for single-cell assay for transposase accessible chromatin (scATAC-seq) using droplet microfluidics that yields essential qualities for high-throughput profiling, including improvements in per-cell library complexity and throughput. This approach enables robust cell-typing of complex tissues and reveals a de novo atlas of cellular and epigenomic diversity across many cell types and cell stages. Overall design: Human isolated bone marrow CD34+ stem/progenitor cells, and isolated peripheral blood CD4+ T cells, CD8+ T cells, Monocytes, B cells and NK cells were were processed using the BioRad SureCell scATAC-seq platform across multiple channels in the instrument.

尽管近年来技术进步已实现单细胞分辨率下的表观基因组图谱绘制，但现有方法的通量与质量仍限制了这些技术的大规模应用。本研究报道了一种基于液滴微流控技术的高通量单细胞转座酶可及性染色质检测（single-cell assay for transposase accessible chromatin, scATAC-seq）平台，该平台具备高通量分析所需的核心性能，包括提升单细胞文库复杂度与检测通量。该方法可实现复杂组织的精准细胞分型，并首次构建出覆盖多种细胞类型与细胞阶段的细胞及表观基因组多样性全新图谱。实验设计概述：本研究采用伯乐（BioRad）SureCell scATAC-seq平台，通过仪器的多个通道对分离得到的人骨髓CD34+干细胞/祖细胞，以及外周血CD4+T细胞、CD8+T细胞、单核细胞、B细胞与NK细胞完成了样本处理。