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Joint profiling of chromatin accessibility and gene expression in thousands of single cells

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Science  28 Sep 2018:
Vol. 361, Issue 6409, pp. 1380-1385
DOI: 10.1126/science.aau0730

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Single-cell chromatin and RNA analysis

Single-cell analyses have begun to provide insight into the differences among and within the individual cells that make up a tissue or organism. However, technological barriers owing to the small amount of material present in each single cell have prevented parallel analyses. Cao et al. present sci-CAR, a pooled barcode method that jointly analyzes both the RNA transcripts and chromatin profiles of single cells. By applying sci-CAR to lung adenocarcinoma cells and mouse kidney tissue, the authors demonstrate precision in assessing expression and genome accessibility at a genome-wide scale. The approach provides an improvement over bulk analysis, which can be confounded by differing cellular subgroups.

Science, this issue p. 1380

Abstract

Although we can increasingly measure transcription, chromatin, methylation, and other aspects of molecular biology at single-cell resolution, most assays survey only one aspect of cellular biology. Here we describe sci-CAR, a combinatorial indexing–based coassay that jointly profiles chromatin accessibility and mRNA (CAR) in each of thousands of single cells. As a proof of concept, we apply sci-CAR to 4825 cells, including a time series of dexamethasone treatment, as well as to 11,296 cells from the adult mouse kidney. With the resulting data, we compare the pseudotemporal dynamics of chromatin accessibility and gene expression, reconstruct the chromatin accessibility profiles of cell types defined by RNA profiles, and link cis-regulatory sites to their target genes on the basis of the covariance of chromatin accessibility and transcription across large numbers of single cells.

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