학술논문
Transcript-indexed ATAC-seq for precision immune profiling
Document Type
article
Author
Satpathy, Ansuman T; Saligrama, Naresha; Buenrostro, Jason D; Wei, Yuning; Wu, Beijing; 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
Source
Nature Medicine. 24(5)
Subject
Language
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.