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

Xingqi Chen, Ulrike M. Litzenburger (), Yuning Wei, Alicia N. Schep, Edward L. LaGory, Hani Choudhry, Amato J. Giaccia, William J. Greenleaf and Howard Y. Chang ()
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Xingqi Chen: Stanford University
Ulrike M. Litzenburger: Stanford University
Yuning Wei: Stanford University
Alicia N. Schep: Stanford University
Edward L. LaGory: Stanford University
Hani Choudhry: King Abdulaziz University
Amato J. Giaccia: Stanford University
William J. Greenleaf: Stanford University
Howard Y. Chang: Stanford University

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07115-y

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