TY - JOUR
T1 - Transcript-indexed ATAC-seq for precision immune profiling
AU - Satpathy, Ansuman T.
AU - Saligrama, Naresha
AU - Buenrostro, Jason D.
AU - Wei, Yuning
AU - Wu, Beijing
AU - Rubin, Adam J.
AU - Granja, Jeffrey M.
AU - Lareau, Caleb A.
AU - Li, Rui
AU - Qi, Yanyan
AU - Parker, Kevin R.
AU - Mumbach, Maxwell R.
AU - Serratelli, William S.
AU - Gennert, David G.
AU - Schep, Alicia N.
AU - Corces, M. Ryan
AU - Khodadoust, Michael S.
AU - Kim, Youn H.
AU - Khavari, Paul A.
AU - Greenleaf, William J.
AU - Davis, Mark M.
AU - Chang, Howard Y.
N1 - Publisher Copyright:
© 2018 Nature America Inc., part of Springer Nature. All rights reserved.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85045857015&partnerID=8YFLogxK
U2 - 10.1038/s41591-018-0008-8
DO - 10.1038/s41591-018-0008-8
M3 - Article
C2 - 29686426
AN - SCOPUS:85045857015
SN - 1078-8956
VL - 24
SP - 580
EP - 590
JO - Nature medicine
JF - Nature medicine
IS - 5
ER -