TY - JOUR
T1 - Characterizing cellular heterogeneity in chromatin state with scCUT&Tag-pro
AU - Zhang, Bingjie
AU - Srivastava, Avi
AU - Mimitou, Eleni
AU - Stuart, Tim
AU - Raimondi, Ivan
AU - Hao, Yuhan
AU - Smibert, Peter
AU - Satija, Rahul
N1 - Funding Information:
We thank all the members of the Satija Lab for thoughtful discussions related to this work. B.Z. is a postdoctoral fellow of the Jane Coffin Childs Memorial Fund for Medical Research. This investigation has been aided by a grant from the Jane Coffin Childs Memorial Fund for Medical Research. This work was supported by the Chan Zuckerberg Initiative (grants EOSS-0000000082 and HCA-A-1704-01895 to R.S.) and the National Institutes of Health (grant K99CA267677-01 to A.S.; grant K99HG011489-01 to T.S.; and grants RM1HG011014-02, 1OT2OD026673-01 and DP2HG009623-01 to R.S.).
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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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U2 - 10.1038/s41587-022-01250-0
DO - 10.1038/s41587-022-01250-0
M3 - Article
C2 - 35332340
AN - SCOPUS:85127098684
JO - Nature Biotechnology
JF - Nature Biotechnology
SN - 1087-0156
ER -