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Transcript-indexed ATAC-seq for precision immune profiling
Open accessAbstract
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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“Importantly, ATAC-seq can be performed in single cells (scATAC-seq), uncovering cell-to-cell variability and rare epigenomic phenotypes (Cusanovich et al., 2018; Satpathy et al., 2018; Buenrostro et al., 2018).”
From Coupled Single-Cell CRISPR Screening and Epigenomic Profiling Reveals Causal Gene Regulatory Networks (2019) · cites this paper as Satpathy et al., 2018
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“Additionally, scATAC-seq profiles can be paired with orthogonal measurements of RNA or protein expression in the same cell (Satpathy et al., 2018; Chen et al., 2018a).”
From Coupled Single-Cell CRISPR Screening and Epigenomic Profiling Reveals Causal Gene Regulatory Networks (2019) · cites this paper as Satpathy et al., 2018
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“previous reports have shown that aggregation of five or more cells is sufficient toaccurately reproduce chromatin accessibility profiles (Satpathy et al., 2018; Schep et al., 2017).”
From Coupled Single-Cell CRISPR Screening and Epigenomic Profiling Reveals Causal Gene Regulatory Networks (2019) · cites this paper as Satpathy et al., 2018
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Self-citationAn Informative Approach to Single-Cell Sequencing Analysis
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Self-citation
Metadata
- 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.
- ORCID
- Satpathy, Ansuman T.
- Saligrama, Naresha
- Buenrostro, Jason D.
- Rubin, Adam J.
- Granja, Jeffrey M.
- Lareau, Caleb A.
- Li, Rui
- Qi, Yanyan
- Parker, Kevin R.
- Mumbach, Maxwell R.
- Serratelli, William S.
- Gennert, David G.
- Schep, Alicia N.
- Corces, M. Ryan
- Khodadoust, Michael S.
- Kim, Youn H.
- Khavari, Paul A.
- Greenleaf, William J.
- 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
- PMC
- PMC5948148
- 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
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- 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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