Cited by 949Single-cell and spatial transcriptomicsGenomics and Chromatin DynamicsGene Regulatory Network Analysis

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

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Cao, Junyue, Cusanovich, Darren A., Ramani, Vijay, Aghamirzaie, Delasa, Pliner, Hannah A., Hill, Andrew J., Daza, Riza M., McFaline-Figueroa, Jose L. +6 more·2018·Science

Abstract

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

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  • Milo may also be useful for single-cell assays beyond scRNA-seq, including multi-omic assays.

    “Milo may also be applicable to single-cell assays other than scRNA-seq, including multi-omic assays [35–39].”
  • Multimodal single-cell approaches are gaining traction within hepatology, allowing combination readouts from the same cell, such as simultaneous acquisition of transcriptomic and epigenomic information.

    “Furthermore, multimodal single-cell approaches are swiftly gaining traction within hepatology, allowing ‘combination readouts’ from the same cell, for example simultaneous acquisition of transcriptomic and epigenomic information, again maximising our ability to identify the key therapeutic targets in pathological cells.165,166”
  • Novel therapeutics developed for one fibrotic disorder may be applicable to a wide range of fibrotic diseases due to shared pathways across organs.

    “Novel therapeutics developed for one fibrotic disorder may be applicable to a wide range of fibrotic diseases due to shared pathways across organs that are uncovered by this work.”

    From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [182]

  • The cardinal identity of a cell is probably already instilled at the postmitotic stage during development, and its subsequent phenotypic differentiation and expression are regulated by extrinsic signals such as cell interactions and neural activity.

    “The cardinal identity of a cell is probably already instilled at the postmitotic stage during development9,61,62,63,64, and its subsequent phenotypic differentiation and expression are regulated by extrinsic signals such as cell interactions and neural activity.”
  • Sci-CAR-seq paired combinatorial indexing with ATAC-seq to examine chromatin states and gene expression together in more than 11,200 nuclei.

    “To achieve higher throughput in single-cell analysis, Sci-CAR-seq combined single-cell combinatorial indexing55 with ATAC-seq to provide deep insights into chromatin states jointly with gene expression in over 11,200 nuclei56.”

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Authors
Cao, J., Cusanovich, D. A., Ramani, V., Aghamirzaie, D., Pliner, H. A., Hill, A. J., Daza, R. M., McFaline-Figueroa, J. L., Packer, J. S., Christiansen, L., Steemers, F. J., Adey, A. C., Trapnell, C., & Shendure, J.
Affiliations
  • University of Washington (US)
  • Department of Genome Sciences, University of Washington, Seattle, WA, USA.
  • Illumina (United States) (US)
  • Oregon Health & Science University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Cusanovich, Darren A.
  • Ramani, Vijay
  • Trapnell, Cole
  • Shendure, Jay
Venue
Science
Published
2018-09-28
Volume
361
Issue
6409
Pages
1380-1385
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2889236955
Cited by
938
References
42
Citations by year
2026: 102 · 2025: 109 · 2024: 113 · 2023: 132 · 2022: 125 · 2021: 156 · 2020: 117 · 2019: 74 · 2018: 9
FWCI
31.93
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Science Foundation (DGE-1256082)
  • National Institutes of Health (DP1HG007811, R01HG006283, DP2 HD088158, R35GM124704)
  • Paul G. Allen Frontiers Foundation
  • Howard Hughes Medical Institute
  • W. M. Keck Foundation
  • Dale. F. Frey Award for Breakthrough Scientists
  • Alfred P. Sloan Foundation Research Fellowship
  • National Heart, Lung, and Blood Institute (T32HL007828)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
Keywords
chromatin accessibility, single-cell transcriptomics, combinatorial indexing, dexamethasone treatment, mouse kidney, cis-regulatory elements, gene expression regulation, single-cell multi-omics
MeSH terms
A549 Cells, Animals, Chromatin, Dexamethasone, Gene Expression Regulation, Humans, Kidney, Transcription, Genetic, Gene Expression Profiling, Genomics, NIH 3T3 Cells, Regulatory Elements, Transcriptional, Mice, HEK293 Cells, Single-Cell Analysis

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