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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 10X 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.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE245957 | GEO | 2023/10/20

REPOSITORIES: GEO

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

Project description:We develop a large-scale single-cell ATAC-seq method (txci-ATAC-seq) by combining Tn5-based pre-indexing with 10X Genomics barcoding. Leveraging this molecular hashing strategy, we demonstrate that txci-ATAC-seq enables the indexing of up to 200,000 nuclei across multiple samples in a single emulsion reaction, representing a ~22-fold increase in throughput compared to the standard workflow at the same collision rate. To improve the multiplexing capability of this new technique, we further develop a "phased" protocol variant (Phased-txci-ATAC-seq) that effectively decouples sample processing from library preparation and has the potential to profile up to 96 samples simultaneously. In this study, 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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