Characterizing cellular heterogeneity in chromatin state with scCUT&Tag-pro
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Abstract
Technologies that profile chromatin modifications at single-cell resolution offer enormous promise for functional genomic characterization, but the sparsity of the measurements and integrating multiple binding maps represent substantial challenges. Here we introduce single-cell (sc)CUT&Tag-pro, a multimodal assay for profiling protein-DNA interactions coupled with the abundance of surface proteins in single cells. In addition, we introduce single-cell ChromHMM, which integrates data from multiple experiments to infer and annotate chromatin states based on combinatorial histone modification patterns. We apply these tools to perform an integrated analysis across nine different molecular modalities in circulating human immune cells. We demonstrate how these two approaches can characterize dynamic changes in the function of individual genomic elements across both discrete cell states and continuous developmental trajectories, nominate associated motifs and regulators that establish chromatin states and identify extensive and cell-type-specific regulatory priming. Finally, we demonstrate how our integrated reference can serve as a scaffold to map and improve the interpretation of additional scCUT&Tag datasets.
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scCUT&TAG-pro is a multimodal method that measures protein-DNA interactions and surface protein levels in individual cells.
“This methodology was further developed into scCUT&TAG-pro, which is a multimodal assay for profiling protein–DNA interactions and the abundance of surface proteins in single cells50.”
From The technological landscape and applications of single-cell multi-omics (2023) · cites this paper as [50]
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- Authors
- Zhang, B., Srivastava, A., Mimitou, E., Stuart, T., Raimondi, I., Hao, Y., Smibert, P., & Satija, R.
- Affiliations
- New York Genome Center (US)
- Corresponding author
- Satija, Rahul
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2022-03-24
- Volume
- 40
- Issue
- 8
- Pages
- 1220-1230
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC9378363
- OpenAlex
- W4221029336
- Cited by
- 104
- References
- 68
- Citations by year
- 2026: 17 · 2025: 14 · 2024: 33 · 2023: 21 · 2022: 19
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Biotechnology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Jane Coffin Childs Memorial Fund for Medical Research
- U.S. Department of Health & Human Services | NIH | National Cancer Institute (K99CA267677-01, K99HG011489-01, DP2HG009623-01)
- U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (RM1HG011014-02)
- U.S. Department of Health & Human Services | NIH | NIH Office of the Director (1OT2OD026673-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- protein-DNA interactions, histone modifications, circulating immune cells, developmental trajectories, regulatory motifs, chromatin accessibility
- MeSH terms
- Chromatin, DNA, Histones, Humans, Genomics, Chromatin Immunoprecipitation
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