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

Item Type:Article
Title:Scalable, multimodal profiling of chromatin accessibility, gene expression and protein levels in single cells
Creators Name:Mimitou, E.P. and Lareau, C.A. and Chen, K.Y. and Zorzetto-Fernandes, A.L. and Hao, Y. and Takeshima, Y. and Luo, W. and Huang, T.S. and Yeung, B.Z. and Papalexi, E. and Thakore, P.I. and Kibayashi, T. and Wing, J.B. and Hata, M. and Satija, R. and Nazor, K.L. and Sakaguchi, S. and Ludwig, L.S. and Sankaran, V.G. and Regev, A. and Smibert, P.
Abstract: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.
Keywords:Cell Differentiation, Chromatin, Cell Lineage, Mitochondrial DNA, Epigenomics, Gene Expression Profiling, Gene Expression Regulation, Hematopoiesis, Mononuclear Leukocytes, Proteins, RNA-Seq, Single-Cell Analysis, T-Lymphocytes, T-Lymphocytes / Metabolism
Source:Nature Biotechnology
Publisher:Nature Publishing Group
Page Range:1246-1258
Date:October 2021
Additional Information:Copyright © The Author(s), under exclusive licence to Springer Nature America, Inc. 2021
Official Publication:https://doi.org/10.1038/s41587-021-00927-2
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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