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

• Published in: Genome Biology Vol. 25; no. 1; pp. 78 - 41
• Main Authors: Zhang, Hao, Mulqueen, Ryan M, Iannuzo, Natalie, Farrera, Dominique O, Polverino, Francesca, Galligan, James J, Ledford, Julie G, Adey, Andrew C, Cusanovich, Darren A
• Format: Journal Article
• Language: English
• Published: England BioMed Central 22.03.2024; BMC
• Subjects: Animals; ATAC-seq; Bar codes; CC16; Cell Nucleus - genetics; Cells; Chromatin; Chromatin - metabolism; Chromatin accessibility; Chromatin Immunoprecipitation Sequencing; Combinatorial indexing; Experiments; Genomes; Genomics; Humans; Mice; Molecular hashing; Regulatory sequences; Regulatory Sequences, Nucleic Acid; Single-cell; Chromatin accessibility; Molecular hashing; CC16; Combinatorial indexing; ATAC-seq; Single-cell
• ISSN: 1474-760X; 1474-7596; 1474-760X
• DOI: 10.1186/s13059-023-03150-1

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.