Cited by 393Genomics and Chromatin DynamicsSingle-cell and spatial transcriptomicsEpigenetics and DNA Methylation

Spatial-CUT&Tag: Spatially resolved chromatin modification profiling at the cellular level

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Deng, Yanxiang, Bartosovic, Marek, Kukanja, Petra, Zhang, Di, Liu, Yang, Su, Graham, Enninful, Archibald, Bai, Zhiliang +2 more·2022·Science

Published version of a preprint

Abstract

Spatial omics emerged as a new frontier of biological and biomedical research. Here, we present spatial-CUT&Tag for spatially resolved genome-wide profiling of histone modifications by combining in situ CUT&Tag chemistry, microfluidic deterministic barcoding, and next-generation sequencing. Spatially resolved chromatin states in mouse embryos revealed tissue-type-specific epigenetic regulations in concordance with ENCODE references and provide spatial information at tissue scale. Spatial-CUT&Tag revealed epigenetic control of the cortical layer development and spatial patterning of cell types determined by histone modification in mouse brain. Single-cell epigenomes can be derived in situ by identifying 20-micrometer pixels containing only one nucleus using immunofluorescence imaging. Spatial chromatin modification profiling in tissue may offer new opportunities to study epigenetic regulation, cell function, and fate decision in normal physiology and pathogenesis.

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  • DBiT-seq was the first reported spatial multi-omics technology to co-map tens of proteins and whole transcriptome.

    “DBiT-seq was the first reported spatial multi-omics technology that demonstrated co-mapping of tens of proteins and with a whole transcriptome, and this method has further expanded to spatial epigenomics profiling of chromatin accessibility124 and histone modification125.”
  • High chromatin silencing score indicates repressed gene expression because of the transcriptional repression function of H3K27me3.

    “High CSS indicates repressed gene expression because of the transcriptional repression function of H3K27me3.”

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Authors
Deng, Y., Bartosovic, M., Kukanja, P., Zhang, D., Liu, Y., Su, G., Enninful, A., Bai, Z., Castelo-Branco, G., & Fan, R.
Affiliations
  • Yale Cancer Center (US)
  • Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.
  • Karolinska Institutet (SE)
  • Yale University (US)
Corresponding author
Fan, Rong
Venue
Science
Published
2022-02-11
Volume
375
Issue
6581
Pages
681-686
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W4211162540
Cited by
393
References
53
Citations by year
2026: 91 · 2025: 92 · 2024: 71 · 2023: 80 · 2022: 48 · 2021: 10 · 2019: 1
FWCI
23.76
Type
journal article
Language
en
Open access
Licence
cc-by-nd
Locations
  • Science (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Yale University
  • Li Ka Shing Foundation
  • Society for Immunotherapy of Cancer
  • National Institutes of Health (1rf1mh128876-01, 2012-38215, UL1TR001863)
  • Stand Up To Cancer
  • National Institute of Mental Health (RF1 MH128876)
  • National Cancer Institute (UH3CA257393, UG3CA257393, U54CA209992, R01CA245313)
  • National Institute of Diabetes and Digestive and Kidney Diseases (U54DK106857)
  • National Center for Advancing Translational Sciences
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 › Epigenetics and DNA Methylation
Keywords
histone modifications, spatial omics, single-cell epigenomics, mouse embryo, immunofluorescence microscopy
MeSH terms
Epigenome, Animals, Brain, Cell Nucleus, Chromatin, Histones, Neurons, Histone Code, Microfluidics, Epigenesis, Genetic, Mice, Single-Cell Analysis, High-Throughput Nucleotide Sequencing

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