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Joint single-cell DNA accessibility and protein epitope profiling reveals environmental regulation of epigenomic heterogeneity

Author

Listed:
  • Xingqi Chen

    (Stanford University
    Karolinska Institutet)

  • Ulrike M. Litzenburger

    (Stanford University)

  • Yuning Wei

    (Stanford University)

  • Alicia N. Schep

    (Stanford University
    Stanford University
    Stanford University)

  • Edward L. LaGory

    (Stanford University)

  • Hani Choudhry

    (King Abdulaziz University)

  • Amato J. Giaccia

    (Stanford University)

  • William J. Greenleaf

    (Stanford University
    Stanford University
    Stanford University)

  • Howard Y. Chang

    (Stanford University
    Stanford University)

Abstract

Here we introduce Protein-indexed Assay of Transposase Accessible Chromatin with sequencing (Pi-ATAC) that combines single-cell chromatin and proteomic profiling. In conjunction with DNA transposition, the levels of multiple cell surface or intracellular protein epitopes are recorded by index flow cytometry and positions in arrayed microwells, and then subject to molecular barcoding for subsequent pooled analysis. Pi-ATAC simultaneously identifies the epigenomic and proteomic heterogeneity in individual cells. Pi-ATAC reveals a casual link between transcription factor abundance and DNA motif access, and deconvolute cell types and states in the tumor microenvironment in vivo. We identify a dominant role for hypoxia, marked by HIF1α protein, in the tumor microvenvironment for shaping the regulome in a subset of epithelial tumor cells.

Suggested Citation

  • Xingqi Chen & Ulrike M. Litzenburger & Yuning Wei & Alicia N. Schep & Edward L. LaGory & Hani Choudhry & Amato J. Giaccia & William J. Greenleaf & Howard Y. Chang, 2018. "Joint single-cell DNA accessibility and protein epitope profiling reveals environmental regulation of epigenomic heterogeneity," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07115-y
    DOI: 10.1038/s41467-018-07115-y
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    Cited by:

    1. Xi Lu & Naga Prathyusha Maturi & Malin Jarvius & Irem Yildirim & Yonglong Dang & Linxuan Zhao & Yuan Xie & E-Jean Tan & Pengwei Xing & Rolf Larsson & Mårten Fryknäs & Lene Uhrbom & Xingqi Chen, 2022. "Cell-lineage controlled epigenetic regulation in glioblastoma stem cells determines functionally distinct subgroups and predicts patient survival," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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