Cited by 68Single-cell and spatial transcriptomicsGenomics and Chromatin DynamicsInnovative Microfluidic and Catalytic Techniques Innovation

Single-cell profiling of proteins and chromatin accessibility using PHAGE-ATAC

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Fiskin, Evgenij, Lareau, Caleb A., Ludwig, Leif S., Eraslan, Gökcen, Liu, Feimei, Ring, Aaron M., Xavier, Ramnik J., Regev, Aviv·2022·Nature Biotechnology

Abstract

Multimodal measurements of single-cell profiles are proving increasingly useful for characterizing cell states and regulatory mechanisms. In the present study, we developed PHAGE-ATAC (Assay for Transposase-Accessible Chromatin), a massively parallel droplet-based method that uses phage displaying, engineered, camelid single-domain antibodies ('nanobodies') for simultaneous single-cell measurements of protein levels and chromatin accessibility profiles, and mitochondrial DNA-based clonal tracing. We use PHAGE-ATAC for multimodal analysis in primary human immune cells, sample multiplexing, intracellular protein analysis and the detection of SARS-CoV-2 spike protein in human cell populations. Finally, we construct a synthetic high-complexity phage library for selection of antigen-specific nanobodies that bind cells of particular molecular profiles, opening an avenue for protein detection, cell characterization and screening with single-cell genomics.

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  • PHAGE-ATAC allows profiling of thousands of single cells while detecting cell-surface proteins, mitochondrial DNA genotypes and epigenomic modifications.

    “This multi-omics method allows profiling of thousands of single cells while reliably detecting cell-surface proteins, mitochondrial DNA genotypes and epigenomic modifications.”

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Authors
Fiskin, E., Lareau, C. A., Ludwig, L. S., Eraslan, G., Liu, F., Ring, A. M., Xavier, R. J., & Regev, A.
Affiliations
  • Stanford Medicine (US)
  • Broad Institute (US)
  • Yale University (US)
Corresponding author
Regev, Aviv
Venue
Nature Biotechnology
Published
2021-10-21
Volume
40
Issue
3
Pages
374-381
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W3206783061
Cited by
68
References
36
Citations by year
2026: 7 · 2025: 9 · 2024: 17 · 2023: 20 · 2022: 10 · 2021: 4
FWCI
4.00
Type
journal article
Language
en
Open access
Locations
  • Nature Biotechnology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • Broad Institute
  • Manton Foundation
  • Ludwig Family Foundation
  • Deutsche Forschungsgemeinschaft (LU 2336/2-1)
  • National Institutes of Health (5rm1hg006193-10)
  • National Human Genome Research Institute (5RM1HG006193, RM1‐HG006193, HG006193)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK043351)
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
  • Physical Sciences › Engineering › Biomedical Engineering › Innovative Microfluidic and Catalytic Techniques Innovation
Keywords
single-cell profiling, chromatin accessibility, nanobodies, phage display, intracellular protein detection, SARS-CoV-2 spike protein detection, human immune cells
MeSH terms
COVID-19, SARS-CoV-2, Bacteriophages, Chromatin, Humans, Single-Cell Analysis, Spike Glycoprotein, Coronavirus

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