High-capacity sample multiplexing for single cell chromatin accessibility profiling

Abstract Single-cell chromatin accessibility has emerged as a powerful means of understanding the epigenetic landscape of diverse tissues and cell types, but profiling cells from many independent specimens is challenging and costly. Here we describe a novel approach, sciPlex-ATAC-seq, which uses unm...

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Main Authors: Gregory T. Booth, Riza M. Daza, Sanjay R. Srivatsan, José L. McFaline-Figueroa, Rula Green Gladden, Andrew C. Mullen, Scott N. Furlan, Jay Shendure, Cole Trapnell
Format: Article
Language:English
Published: BMC 2023-12-01
Series:BMC Genomics
Subjects:
Online Access:https://doi.org/10.1186/s12864-023-09832-1
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author Gregory T. Booth
Riza M. Daza
Sanjay R. Srivatsan
José L. McFaline-Figueroa
Rula Green Gladden
Andrew C. Mullen
Scott N. Furlan
Jay Shendure
Cole Trapnell
author_facet Gregory T. Booth
Riza M. Daza
Sanjay R. Srivatsan
José L. McFaline-Figueroa
Rula Green Gladden
Andrew C. Mullen
Scott N. Furlan
Jay Shendure
Cole Trapnell
author_sort Gregory T. Booth
collection DOAJ
description Abstract Single-cell chromatin accessibility has emerged as a powerful means of understanding the epigenetic landscape of diverse tissues and cell types, but profiling cells from many independent specimens is challenging and costly. Here we describe a novel approach, sciPlex-ATAC-seq, which uses unmodified DNA oligos as sample-specific nuclear labels, enabling the concurrent profiling of chromatin accessibility within single nuclei from virtually unlimited specimens or experimental conditions. We first demonstrate our method with a chemical epigenomics screen, in which we identify drug-altered distal regulatory sites predictive of compound- and dose-dependent effects on transcription. We then analyze cell type-specific chromatin changes in PBMCs from multiple donors responding to synthetic and allogeneic immune stimulation. We quantify stimulation-altered immune cell compositions and isolate the unique effects of allogeneic stimulation on chromatin accessibility specific to T-lymphocytes. Finally, we observe that impaired global chromatin decondensation often coincides with chemical inhibition of allogeneic T-cell activation.
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spelling doaj.art-11167b29a9ec4b1fa5f656373a3275ff2023-12-10T12:08:53ZengBMCBMC Genomics1471-21642023-12-0124112310.1186/s12864-023-09832-1High-capacity sample multiplexing for single cell chromatin accessibility profilingGregory T. Booth0Riza M. Daza1Sanjay R. Srivatsan2José L. McFaline-Figueroa3Rula Green Gladden4Andrew C. Mullen5Scott N. Furlan6Jay Shendure7Cole Trapnell8Department of Genome Sciences, University of WashingtonDepartment of Genome Sciences, University of WashingtonDepartment of Genome Sciences, University of WashingtonDepartment of Genome Sciences, University of WashingtonDepartment of Genome Sciences, University of WashingtonDepartment of Genome Sciences, University of WashingtonClinical Research Division, Fred Hutchinson Cancer Research CenterDepartment of Genome Sciences, University of WashingtonDepartment of Genome Sciences, University of WashingtonAbstract Single-cell chromatin accessibility has emerged as a powerful means of understanding the epigenetic landscape of diverse tissues and cell types, but profiling cells from many independent specimens is challenging and costly. Here we describe a novel approach, sciPlex-ATAC-seq, which uses unmodified DNA oligos as sample-specific nuclear labels, enabling the concurrent profiling of chromatin accessibility within single nuclei from virtually unlimited specimens or experimental conditions. We first demonstrate our method with a chemical epigenomics screen, in which we identify drug-altered distal regulatory sites predictive of compound- and dose-dependent effects on transcription. We then analyze cell type-specific chromatin changes in PBMCs from multiple donors responding to synthetic and allogeneic immune stimulation. We quantify stimulation-altered immune cell compositions and isolate the unique effects of allogeneic stimulation on chromatin accessibility specific to T-lymphocytes. Finally, we observe that impaired global chromatin decondensation often coincides with chemical inhibition of allogeneic T-cell activation.https://doi.org/10.1186/s12864-023-09832-1Single-cellSequencingGenomicsChromatinPerturbationScreening
spellingShingle Gregory T. Booth
Riza M. Daza
Sanjay R. Srivatsan
José L. McFaline-Figueroa
Rula Green Gladden
Andrew C. Mullen
Scott N. Furlan
Jay Shendure
Cole Trapnell
High-capacity sample multiplexing for single cell chromatin accessibility profiling
BMC Genomics
Single-cell
Sequencing
Genomics
Chromatin
Perturbation
Screening
title High-capacity sample multiplexing for single cell chromatin accessibility profiling
title_full High-capacity sample multiplexing for single cell chromatin accessibility profiling
title_fullStr High-capacity sample multiplexing for single cell chromatin accessibility profiling
title_full_unstemmed High-capacity sample multiplexing for single cell chromatin accessibility profiling
title_short High-capacity sample multiplexing for single cell chromatin accessibility profiling
title_sort high capacity sample multiplexing for single cell chromatin accessibility profiling
topic Single-cell
Sequencing
Genomics
Chromatin
Perturbation
Screening
url https://doi.org/10.1186/s12864-023-09832-1
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