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Multiplex single-cell profiling of chromatin accessibility by combinatorial cellular indexing

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Science  22 May 2015:
Vol. 348, Issue 6237, pp. 910-914
DOI: 10.1126/science.aab1601

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Chromatin state and the single cell

Identifying the chromatin state of any single cell, which may or may not have a different function or represent different stages relative to others collected within any single culture, experiment, or tissue, has been challenging. Cusanovitch et al. skirted previously identified technological limitations to identify regions of accessible chromatin at single-cell resolution. Combinatorial cellular indexing, a strategy for multiplex barcoding of thousands of single cells per experiment, was successfully used to investigate the genome-wide chromatin accessibility landscape in each of over 15,000 single cells.

Science, this issue p. 910

Abstract

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 before 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 more than 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.

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