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

Hao Zhang; Ryan M. Mulqueen; Natalie Iannuzo; Dominique O. Farrera; Francesca Polverino; James J. Galligan; Julie G. Ledford; Andrew C. Adey; Darren A. Cusanovich

doi:10.1186/s13059-023-03150-1

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

Hao Zhang, Ryan M. Mulqueen, Natalie Iannuzo, Dominique O. Farrera, Francesca Polverino, James J. Galligan, Julie G. Ledford, Andrew C. Adey, Darren A. Cusanovich

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	78
Journal	Genome biology
Volume	25
Issue number	1
DOIs	https://doi.org/10.1186/s13059-023-03150-1
State	Published - Dec 2024

Keywords

ATAC-seq
CC16
Chromatin accessibility
Combinatorial indexing
Molecular hashing
Single-cell

ASJC Scopus subject areas

Ecology, Evolution, Behavior and Systematics
Genetics
Cell Biology

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10.1186/s13059-023-03150-1

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title = "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, 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.",

keywords = "ATAC-seq, CC16, Chromatin accessibility, Combinatorial indexing, Molecular hashing, Single-cell",

author = "Hao Zhang and Mulqueen, {Ryan M.} and Natalie Iannuzo and Farrera, {Dominique O.} and Francesca Polverino and Galligan, {James J.} and Ledford, {Julie G.} and Adey, {Andrew C.} and Cusanovich, {Darren A.}",

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doi = "10.1186/s13059-023-03150-1",

language = "English (US)",

volume = "25",

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AU - Zhang, Hao

AU - Mulqueen, Ryan M.

AU - Iannuzo, Natalie

AU - Farrera, Dominique O.

AU - Polverino, Francesca

AU - Galligan, James J.

AU - Ledford, Julie G.

AU - Adey, Andrew C.

AU - Cusanovich, Darren A.

N1 - Publisher Copyright: © The Author(s) 2024.

PY - 2024/12

Y1 - 2024/12

N2 - 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.

AB - 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.

KW - ATAC-seq

KW - CC16

KW - Chromatin accessibility

KW - Combinatorial indexing

KW - Molecular hashing

KW - Single-cell

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JF - Genome biology

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

Abstract

Keywords

ASJC Scopus subject areas

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