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 journalArticlepeer-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 languageEnglish (US)
Article number78
JournalGenome biology
Volume25
Issue number1
DOIs
StatePublished - 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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