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

ABSTRACT: High-throughput combinatorial indexing enables scalable single-cell chromatin accessibility profiling [PBMC]

PROVIDER: PRJNA509255 | ENA |

REPOSITORIES: ENA

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

Project description: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.

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Project description:Technical advances have enabled the collection of genome and transcriptome data sets with single-cell resolution. However, single-cell characterization of the epigenome has remained challenging. Furthermore, because cells must be physically separated prior to biochemical processing, conventional single-cell preparatory methods scale linearly. We applied combinatorial cellular indexing to measure chromatin accessibility in thousands of single cells per assay, circumventing the need for compartmentalization of individual cells. We report chromatin accessibility profiles from over 15,000 single cells and use these data to cluster cells on the basis of chromatin accessibility landscapes. We identify modules of coordinately regulated chromatin accessibility at the level of single cells both between and within cell types, with a scalable method that may accelerate progress toward a human cell atlas. 3 replicates from GM12878 and HL-60 cell lines collected for differential gene expression analysis.

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