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

eLife

Lucas T Graybuck¹  Thomas F Bumol¹  Palak C Genge¹  Elliott Swanson¹  Peter J Skene¹  Cara Lord¹  Alexander T Heubeck¹  Adam K Savage¹  Julian Reading¹  Zachary Thomson¹  Morgan DA Weiss¹  Xiao-jun Li¹  Richard R Green²  Troy R Torgerson³ 

[1] Allen Institute for Immunology, Seattle, United States;Allen Institute for Immunology, Seattle, United States;Department of Biomedical Informatics and Medical Education (BIME), University of Washington, Seattle, United States;Allen Institute for Immunology, Seattle, United States;Department of Pediatrics, University of Washington, Seattle, United States;

关键词: transcription;    chromatin;    epitopes;    sequencing;    genomics;    multiomics;    Human;   

DOI  :  10.7554/eLife.63632

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY