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

By Junyue Cao, D. Cusanovich, V. Ramani, Delasa Aghamirzaie, Hannah A. Pliner, Andrew J. Hill, R. Daza, J. McFaline-Figueroa, Jonathan S. Packer, Lena Christiansen and 4 more. Science, 2018

822 citations recorded by the source corpus.

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 A technique termed sci-CAR can assess both chromatin accessibility and RNA transcription at the single-cell level. 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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a25234b8620971dbc77dce111be391862113105d

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Citations in the corpus

Computational principles and challenges in single-cell data integration (2021, methodology): “Similarly, the first parallel RNA expression, DNA methylation and/or chromatin accessibility assays have been used to probe dependencies between proximal regulatory elements and gene expression levels 3,6,37–39 .”
Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin (2020, methodology): “SHARE-seq also consistently outperformed previously published joint ATAC-RNA approaches (Cao et al., 2018; Chen et al., 2019; Zhu et al., 2019; Figure 1E).”
Methods and applications for single-cell and spatial multi-omics (2023, neutral): “Examples include scCAT-seq 35 and Smart3-ATAC 36 , which are plate-based; sci-CAR-seq 37 , SHARE-seq 38 , SNARE-seq2 39 and Paired-seq 40 (Fig.”
Single-cell chromatin state analysis with Signac (2021, background): “The measurement of both gene expression and DNA accessibility in the same cell creates an opportunity to link noncoding DNA elements to their potential regulatory targets through the correlation between DNA accessibility and the expression of a nearby gene 12,17,20 .”
DNA methylation aging clocks: challenges and recommendations (2019, methodology): “The technology is rapidly developing, as illustrated by the recent sci-CAR (single-cell combinatorial indexing chromatin accessibility and mRNA) assay, permitting the profiling of both chromatin accessibility and gene expression in thousands of single cells [190].”
Integrated analysis of multimodal single-cell data (2020, neutral): “For example, recent developments have enabled the simultaneous measurement of ATAC-seq profiles and transcriptomes from single nuclei (Cao et al., 2018; Chen et al., 2019b).”
Best practices for single-cell analysis across modalities (2023, background): “Holistic representations of cells can be obtained only with analyses across modalities 245 , whereby several modalities of the same cells are jointly examined.”