Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion

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Authors Kathryn E. Yost, Ansuman T. Satpathy, Daniel K. Wells, Yanyan Qi, Chunlin Wang, Robin Kageyama, Katherine McNamara, Jeffrey M. Granja, Kavita Y. Sarin, Ryanne A. Brown, Rohit K. Gupta, Christina Curtis, Samantha L. Bucktrout, Mark M. Davis, Anne Lynn S. Chang, Howard Y. Chang
Journal/Conference Name Granja
Paper Category
Paper Abstract Understanding complex tissues requires single-cell deconstruction of gene regulation with precision and scale. Here, we assess the performance of a massively parallel droplet-based method for mapping transposase-accessible chromatin in single cells using sequencing (scATAC-seq). We apply scATAC-seq to obtain chromatin profiles of more than 200,000 single cells in human blood and basal cell carcinoma. In blood, application of scATAC-seq enables marker-free identification of cell type-specific cis- and trans-regulatory elements, mapping of disease-associated enhancer activity and reconstruction of trajectories of cellular differentiation. In basal cell carcinoma, application of scATAC-seq reveals regulatory networks in malignant, stromal and immune cells in the tumor microenvironment. Analysis of scATAC-seq profiles from serial tumor biopsies before and after programmed cell death protein 1 blockade identifies chromatin regulators of therapy-responsive T cell subsets and reveals a shared regulatory program that governs intratumoral CD8+ T cell exhaustion and CD4+ T follicular helper cell development. We anticipate that scATAC-seq will enable the unbiased discovery of gene regulatory factors across diverse biological systems.
Date of publication 2019
Code Programming Language R
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