Cited by 156Single-cell and spatial transcriptomicsGenomics and Chromatin DynamicsT-cell and B-cell Immunology

Transcript-indexed ATAC-seq for precision immune profiling

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Satpathy, Ansuman T., Saligrama, Naresha, Buenrostro, Jason D., Wei, Yuning, Wu, Beijing, Rubin, Adam J., Granja, Jeffrey M., Lareau, Caleb A. +14 more·2018·Nature Medicine

Abstract

T cells create vast amounts of diversity in the genes that encode their T cell receptors (TCRs), which enables individual clones to recognize specific peptide-major histocompatibility complex (MHC) ligands. Here we combined sequencing of the TCR-encoding genes with assay for transposase-accessible chromatin with sequencing (ATAC-seq) analysis at the single-cell level to provide information on the TCR specificity and epigenomic state of individual T cells. By using this approach, termed transcript-indexed ATAC-seq (T-ATAC-seq), we identified epigenomic signatures in immortalized leukemic T cells, primary human T cells from healthy volunteers and primary leukemic T cells from patient samples. In peripheral blood CD4+ T cells from healthy individuals, we identified cis and trans regulators of naive and memory T cell states and found substantial heterogeneity in surface-marker-defined T cell populations. In patients with a leukemic form of cutaneous T cell lymphoma, T-ATAC-seq enabled identification of leukemic and nonleukemic regulatory pathways in T cells from the same individual by allowing separation of the signals that arose from the malignant clone from the background T cell noise. Thus, T-ATAC-seq is a new tool that enables analysis of epigenomic landscapes in clonal T cells and should be valuable for studies of T cell malignancy, immunity and immunotherapy.

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Authors
Satpathy, A. T., Saligrama, N., Buenrostro, J. D., Wei, Y., Wu, B., Rubin, A. J., Granja, J. M., Lareau, C. A., Li, R., Qi, Y., Parker, K. R., Mumbach, M. R., Serratelli, W. S., Gennert, D. G., Schep, A. N., Corces, M. R., Khodadoust, M. S., Kim, Y. H., Khavari, P. A., Greenleaf, W. J., Davis, M. M., & Chang, H. Y.
Affiliations
  • Stanford Medicine (US)
  • Broad Institute (US)
  • Chan Zuckerberg Biohub San Francisco (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Davis, Mark M.
  • Chang, Howard Y.
Venue
Nature Medicine
Published
2018-04-23
Volume
24
Issue
5
Pages
580-590
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W2801515322
Cited by
152
References
64
Citations by year
2026: 7 · 2025: 6 · 2024: 8 · 2023: 18 · 2022: 15 · 2021: 35 · 2020: 36 · 2019: 21 · 2018: 5
FWCI
8.89
Type
journal article
Language
en
Open access
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health (1s10od018220-01)
  • National Human Genome Research Institute (P50HG007735, T32HG000044)
  • National Institute of General Medical Sciences (T32GM008294)
  • National Institute of Allergy and Infectious Diseases (U19AI057229)
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 › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
T cell receptor, single-cell epigenomics, T cell receptor diversity, T cell heterogeneity, naive and memory T cells, CD4+ T cells, cutaneous T-cell lymphoma, leukemic T cells, chromatin accessibility, T-cell malignancies, T cell clones, immunotherapy
MeSH terms
Cell Line, Transformed, Chromatin, Clone Cells, Humans, Immunity, Leukemia, Receptors, Antigen, T-Cell, RNA, Messenger, CD4-Positive T-Lymphocytes, Jurkat Cells, Transposases, Epigenomics, Single-Cell Analysis, High-Throughput Nucleotide Sequencing

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