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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

摘要

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.