期刊
NATURE BIOTECHNOLOGY
卷 39, 期 10, 页码 1246-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41587-021-00927-2
关键词
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资金
- Broad Institute
- Whitehead Institute Flow Cytometry Core facilities
- National Institutes of Health [R01 DK103794, R01 HL146500]
- National Institutes of Health/National Human Genome Research Institute [R21 HG-009748, RM1 HG0110014]
- Japan Society for Promotion of Science for Specially Promoted Research [16H06295]
- Japan Agency for Medical Research and Development for Leading Advanced Projects for Medical Innovation
- New York Stem Cell Foundation (NYSCF)
- Howard Hughes Medical Institute
- Chan Zuckerberg Initiative/Silicon Valley Community Foundation Human Cell Atlas grant [HCA3-0000000309]
- Stanford Science Fellowship
- Emmy Noether fellowship by the German Research Foundation [LU 2336/2-1]
- Klarman Cell Observatory
ASAP-seq is a new tool that can simultaneously profile chromatin accessibility and protein levels in single cells. It uses a bridging approach that repurposes antibody:oligonucleotide conjugates originally designed for protein measurements paired with single-cell RNA sequencing. Together with DOGMA-seq, it demonstrates the utility of systematic multi-omic profiling by revealing coordinated and distinct changes in chromatin, RNA, and surface proteins in single cells.
Recent technological advances have enabled massively parallel chromatin profiling with scATAC-seq (single-cell assay for transposase accessible chromatin by sequencing). Here we present ATAC with select antigen profiling by sequencing (ASAP-seq), a tool to simultaneously profile accessible chromatin and protein levels. Our approach pairs sparse scATAC-seq data with robust detection of hundreds of cell surface and intracellular protein markers and optional capture of mitochondrial DNA for clonal tracking, capturing three distinct modalities in single cells. ASAP-seq uses a bridging approach that repurposes antibody:oligonucleotide conjugates designed for existing technologies that pair protein measurements with single-cell RNA sequencing. Together with DOGMA-seq, an adaptation of CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) for measuring gene activity across the central dogma of gene regulation, we demonstrate the utility of systematic multi-omic profiling by revealing coordinated and distinct changes in chromatin, RNA and surface proteins during native hematopoietic differentiation and peripheral blood mononuclear cell stimulation and as a combinatorial decoder and reporter of multiplexed perturbations in primary T cells. Chromatin accessibility, gene expression and protein levels are measured in the same single cell.
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