biostudies-literatureZhang HNational Institute of Environmental Health SciencesNIEHS NIH HHSNIMH NIH HHSNHLBI NIH HHSNational Heart, Lung, and Blood InstituteNational Institute of Mental HealthNational Institute of General Medical SciencesNIGMS NIH HHS78https://www.ebi.ac.uk/biostudies/studies/S-EPMC10958877biostudies-literatureUnknown25(1)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.Genome biologytxci-ATAC-seq: a massive-scale single-cell technique to profile chromatin accessibility.PMC10958877R35 GM137896RF1 MH128842R35 GM137910T32 ES007091T32ES007091R35GM124704RF1MH128842R35 GM124704R01 HL142769R35GM137910R01HL142769R35GM137896P30 ES006694Cusanovich DAGalligan JJIannuzo NZhang HMulqueen RMPolverino FFarrera DOLedford JGAdey ACfalsetxci-ATAC-seq: a massive-scale single-cell technique to profile chromatin accessibility.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.2024-01-01T00:00:00Z2024 Mar2026-06-02T10:38:00.702Z2025-04-06T00:49:25.834ZS-EPMC109588773851997910.1186/s13059-023-03150-1