Scalable, multimodal profiling of chromatin accessibility, gene expression and protein levels in single cells.

Scalable, multimodal profiling of chromatin accessibility, gene expression and protein levels in single cells.
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DOI:
10.1038/s41587-021-00927-2
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发表时间:
2021-10
影响因子:
46.9
通讯作者:
Smibert P
Smibert P
中科院分区:
工程技术1区
文献类型:
--
作者:
Mimitou EP;Lareau CA;Chen KY;Zorzetto-Fernandes AL;Hao Y;Takeshima Y;Luo W;Huang TS;Yeung BZ;Papalexi E;Thakore PI;Kibayashi T;Wing JB;Hata M;Satija R;Nazor KL;Sakaguchi S;Ludwig LS;Sankaran VG;Regev A;Smibert P

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Recent technological advances have enabled massively parallel chromatin profiling with single-cell Assay for Transposase Accessible Chromatin by sequencing (scATAC-seq) in thousands of individual cells. Here, we extend these approaches and 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 (mtDNA) for clonal tracking, thus concomitantly capturing three distinct modalities in single cells. Importantly, ASAP-seq uses a novel bridging approach that repurposes antibody:oligo conjugates designed for existing technologies that pair protein measurements with single cell RNA-seq. Together with DOGMA-seq, a novel adaptation of our existing CITE-seq method 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, peripheral blood mononuclear cell stimulation, and as a combinatorial decoder and reporter of multiplexed perturbations in primary T cells.
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