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

By Ansuman T. Satpathy, Jeffrey M. Granja, K. Yost, Yanyan Qi, Francesca Meschi, Geoffrey P. McDermott, B. Olsen, Maxwell R Mumbach, Sarah E. Pierce, M. Corces and 12 more. Nature Biotechnology, 2019

858 citations recorded by the source corpus.

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. A droplet-based single-cell ATAC-seq method enables rapid mapping of chromatin accessibility in tens of thousands of cells.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/c2443710a6665d03e7de6aea806806cd5b344705

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Citations in the corpus

• Pan-cancer single-cell landscape of tumor-infiltrating T cells (2021, background): “Supporting such TOX regulation, a reanalysis of single-cell assay for transposase-accessible chromatin with high-throughput sequencing (scATAC-seq) data of basal cell carcinoma (36) revealed that the high-accessibility peaks in the promoter or distinct intragenic enhancer of TOX in the terminal Tex ”
• Comprehensive analysis of single cell ATAC-seq data with SnapATAC (2021, methodology): “More recently, single-cell ATAC-seq analysis has been demonstrated on droplet-based platforms 12,13 , enabling pro fi ling of chromatin accessibility from hundreds of thousands cells in a single experiment 13 .”
• Identifying phenotype-associated subpopulations by integrating bulk and single-cell sequencing data (2021, positive): “Furthermore, although we only conducted the integration of bulk gene expressions with scRNA-seq data, Scissor can also be applied to other single-cell measurements like chromatin accessibility 48 and DNA methylation 49 .”
• Assessment of computational methods for the analysis of single-cell ATAC-seq data (2019, result): “As observed in other studies [1, 25], these results suggest calling peaks on PB-All may 865 result in sub-optimal performance.”