Transcript-indexed ATAC-seq reveals paired single-cell T cell receptor identity and chromatin accessibility for precision immune profiling [Ensembl]

T cells create vast amounts of diversity in their T cell receptor (TCR) genes, enabling individual clones to recognize particular peptide-MHC ligands. Here we combine transposase accessible chromatin analysis and TCR sequencing (T-ATAC-seq) at the single-cell level. Using this approach, we identify epigenomic signatures in immortalized leukemic T cells, primary human T cells from healthy volunteers, and primary leukemic T cells from clinical patient samples. In healthy peripheral blood CD4+ T cells, we identify cis and trans regulators of naive and memory T cell states and find significant heterogeneity in surface marker-defined populations. In patients with cutaneous T cell lymphoma, we identify leukemic and non-leukemic regulatory pathways in cells from the same individual, which has been previously challenging. Thus, T-ATAC-seq is a new tool enabling analysis of epigenomic landscapes in clonal T cells and should be valuable for studies of T cell malignancy, immunity, and immunotherapy. Overall design: CD4+ T cell subsets were sorted form peripheral blood of healthy human volunteers. 50-60,000 cells from each subset were subject to open chromatin ATAC-seq profiling. Samples include 2 or 3 biological replicates from Naïve CD4+ T cells, CD4+ T helper 1 (TH1) cells, CD4+ T helper 2 (TH2) cells, CD4+ T helper 17 (TH17) cells, CD4+ T helper 1-17 (TH1-17) cells, and T regulatory cells (TREG).