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...
Main Authors: | , , , , , , , , |
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Format: | Article |
Language: | English |
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BMC
2023-12-01
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Series: | BMC Genomics |
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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. |
first_indexed | 2024-03-09T01:21:09Z |
format | Article |
id | doaj.art-11167b29a9ec4b1fa5f656373a3275ff |
institution | Directory Open Access Journal |
issn | 1471-2164 |
language | English |
last_indexed | 2024-03-09T01:21:09Z |
publishDate | 2023-12-01 |
publisher | BMC |
record_format | Article |
series | BMC Genomics |
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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