Simultaneous trimodal single-cell measurement of transcripts, epitopes, and chromatin accessibility using TEA-seq

• Published in: eLife Vol. 10
• Main Authors: Swanson, Elliott, Lord, Cara, Reading, Julian, Heubeck, Alexander T, Genge, Palak C, Thomson, Zachary, Weiss, Morgan DA, Li, Xiao-Jun, Savage, Adam K, Green, Richard R, Torgerson, Troy R, Bumol, Thomas F, Graybuck, Lucas T, Skene, Peter J
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 09.04.2021; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Antigenic determinants; B cells; Cell differentiation; Cell surface; Chromatin; Epigenetics; Epitopes; Experiments; Flow cytometry; Gene regulation; Genetics and Genomics; genomics; Immunology and Inflammation; multiomics; Neutrophils; Peripheral blood; Quality control; Scientific equipment and supplies industry; sequencing; Surface markers; Tools and Resources; transcription; Transcriptomics; Canada; United States; epitopes; genetics; transcription; inflammation; genomics; multiomics; chromatin; human; immunology; sequencing
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.63632

Single-cell measurements of cellular characteristics have been instrumental in understanding the heterogeneous pathways that drive differentiation, cellular responses to signals, and human disease. Recent advances have allowed paired capture of protein abundance and transcriptomic state, but a lack of epigenetic information in these assays has left a missing link to gene regulation. Using the heterogeneous mixture of cells in human peripheral blood as a test case, we developed a novel scATAC-seq workflow that increases signal-to-noise and allows paired measurement of cell surface markers and chromatin accessibility: integrated cellular indexing of chromatin landscape and epitopes, called ICICLE-seq. We extended this approach using a droplet-based multiomics platform to develop a trimodal assay that simultaneously measures transcriptomics (scRNA-seq), epitopes, and chromatin accessibility (scATAC-seq) from thousands of single cells, which we term TEA-seq. Together, these multimodal single-cell assays provide a novel toolkit to identify type-specific gene regulation and expression grounded in phenotypically defined cell types.