txci-ATAC-seq: a massive-scale single-cell technique to profile chromatin accessibility

Abstract We develop a large-scale single-cell ATAC-seq method by combining Tn5-based pre-indexing with 10× Genomics barcoding, enabling the indexing of up to 200,000 nuclei across multiple samples in a single reaction. We profile 449,953 nuclei across diverse tissues, including the human cortex, mou...

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Main Authors: Hao Zhang, Ryan M. Mulqueen, Natalie Iannuzo, Dominique O. Farrera, Francesca Polverino, James J. Galligan, Julie G. Ledford, Andrew C. Adey, Darren A. Cusanovich
Format: Article
Language:English
Published: BMC 2024-03-01
Series:Genome Biology
Subjects:
Online Access:https://doi.org/10.1186/s13059-023-03150-1
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author Hao Zhang
Ryan M. Mulqueen
Natalie Iannuzo
Dominique O. Farrera
Francesca Polverino
James J. Galligan
Julie G. Ledford
Andrew C. Adey
Darren A. Cusanovich
author_facet Hao Zhang
Ryan M. Mulqueen
Natalie Iannuzo
Dominique O. Farrera
Francesca Polverino
James J. Galligan
Julie G. Ledford
Andrew C. Adey
Darren A. Cusanovich
author_sort Hao Zhang
collection DOAJ
description Abstract We develop a large-scale single-cell ATAC-seq method by combining Tn5-based pre-indexing with 10× Genomics barcoding, enabling the indexing of up to 200,000 nuclei across multiple samples in a single reaction. We profile 449,953 nuclei across diverse tissues, including the human cortex, mouse brain, human lung, mouse lung, mouse liver, and lung tissue from a club cell secretory protein knockout (CC16−/−) model. Our study of CC16−/− nuclei uncovers previously underappreciated technical artifacts derived from remnant 129 mouse strain genetic material, which cause profound cell-type-specific changes in regulatory elements near many genes, thereby confounding the interpretation of this commonly referenced mouse model.
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spelling doaj.art-45dac0a06c854b82a3eca3eae9b2d3592024-03-24T12:22:25ZengBMCGenome Biology1474-760X2024-03-0125114110.1186/s13059-023-03150-1txci-ATAC-seq: a massive-scale single-cell technique to profile chromatin accessibilityHao Zhang0Ryan M. Mulqueen1Natalie Iannuzo2Dominique O. Farrera3Francesca Polverino4James J. Galligan5Julie G. Ledford6Andrew C. Adey7Darren A. Cusanovich8Department of Cellular and Molecular Medicine, University of ArizonaDepartment of Molecular and Medical Genetics, Oregon Health & Science UniversityDepartment of Cellular and Molecular Medicine, University of ArizonaDepartment of Pharmacology and Toxicology, University of ArizonaAsthma & Airway Disease Research Center, University of ArizonaDepartment of Pharmacology and Toxicology, University of ArizonaDepartment of Cellular and Molecular Medicine, University of ArizonaDepartment of Molecular and Medical Genetics, Oregon Health & Science UniversityDepartment of Cellular and Molecular Medicine, University of ArizonaAbstract We develop a large-scale single-cell ATAC-seq method by combining Tn5-based pre-indexing with 10× Genomics barcoding, enabling the indexing of up to 200,000 nuclei across multiple samples in a single reaction. We profile 449,953 nuclei across diverse tissues, including the human cortex, mouse brain, human lung, mouse lung, mouse liver, and lung tissue from a club cell secretory protein knockout (CC16−/−) model. Our study of CC16−/− nuclei uncovers previously underappreciated technical artifacts derived from remnant 129 mouse strain genetic material, which cause profound cell-type-specific changes in regulatory elements near many genes, thereby confounding the interpretation of this commonly referenced mouse model.https://doi.org/10.1186/s13059-023-03150-1Single-cellATAC-seqChromatin accessibilityCombinatorial indexingMolecular hashingCC16
spellingShingle Hao Zhang
Ryan M. Mulqueen
Natalie Iannuzo
Dominique O. Farrera
Francesca Polverino
James J. Galligan
Julie G. Ledford
Andrew C. Adey
Darren A. Cusanovich
txci-ATAC-seq: a massive-scale single-cell technique to profile chromatin accessibility
Genome Biology
Single-cell
ATAC-seq
Chromatin accessibility
Combinatorial indexing
Molecular hashing
CC16
title txci-ATAC-seq: a massive-scale single-cell technique to profile chromatin accessibility
title_full txci-ATAC-seq: a massive-scale single-cell technique to profile chromatin accessibility
title_fullStr txci-ATAC-seq: a massive-scale single-cell technique to profile chromatin accessibility
title_full_unstemmed txci-ATAC-seq: a massive-scale single-cell technique to profile chromatin accessibility
title_short txci-ATAC-seq: a massive-scale single-cell technique to profile chromatin accessibility
title_sort txci atac seq a massive scale single cell technique to profile chromatin accessibility
topic Single-cell
ATAC-seq
Chromatin accessibility
Combinatorial indexing
Molecular hashing
CC16
url https://doi.org/10.1186/s13059-023-03150-1
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