Transcript-indexed ATAC-seq for precision immune profiling.

Autor: Satpathy AT; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA., Saligrama N; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA., Buenrostro JD; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.; Harvard Society of Fellows, Harvard University, Cambridge, MA, USA., Wei Y; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.; Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA., Wu B; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Rubin AJ; Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA., Granja JM; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.; Biophysics Program, Stanford University School of Medicine, Stanford, CA, USA., Lareau CA; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA., Li R; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.; Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA., Qi Y; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.; Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA., Parker KR; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.; Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA., Mumbach MR; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Serratelli WS; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA., Gennert DG; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Schep AN; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Corces MR; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.; Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA., Khodadoust MS; Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA., Kim YH; Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA., Khavari PA; Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA., Greenleaf WJ; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.; Department of Applied Physics, Stanford University, Stanford, CA, USA.; Chan Zuckerberg Biohub, San Francisco, CA, USA., Davis MM; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA. mmdavis@stanford.edu.; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA. mmdavis@stanford.edu.; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA. mmdavis@stanford.edu., Chang HY; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA. howchang@stanford.edu.; Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA. howchang@stanford.edu.; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA. howchang@stanford.edu.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2018 May; Vol. 24 (5), pp. 580-590. Date of Electronic Publication: 2018 Apr 23.
DOI: 10.1038/s41591-018-0008-8
Abstrakt: 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.
Databáze: MEDLINE
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