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

Abstract

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.

Optimized workflow for human PBMC multiomic immunosurveillance studies

“…Data analysis for the scRNA-seq and integration of data sets are not encompassed within this protocol but are described in Savage et al. (2021) , Swanson et al (2021) and Talla et al. (2021) .…”

Why Single-Cell Sequencing Has Promise in MDS

“…First, ATAC with select antigen profiling by sequencing (ASAP-seq) explored fixation to retain surface-bound ADT during nuclei permeabilized for TN5 transposition but lacks RNA capture ( 31 ). Second, fixation-free single-cell tri-modal information capture of Transcriptome, Epitopes and ATAC (TEA-seq) was established by Swanson et al ( 32 ). Chen et al.…”

singlecellVR: Interactive Visualization of Single-Cell Data in Virtual Reality

“…Additionally, assays to profile DNA methylation (Luo et al, 2018) or protein levels are now maturing and becoming more widely-accessible (Specht et al, 2019;Labib and Kelley, 2020). Most recently, combinations of various data modalities can now routinely be collected in parallel from the same cell (Chen S. et al, 2019;Zhu et al, 2019;Ma et al, 2020;Xing et al, 2020;Swanson et al, 2021).…”