RT Journal Article
SR Electronic
T1 Joint single-cell DNA accessibility and protein epitope profiling reveals environmental regulation of epigenomic heterogeneity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 310359
DO 10.1101/310359
A1 Xingqi Chen
A1 Ulrike M. Litzenburger
A1 Yuning Wei
A1 Alicia N. Schep
A1 Edward L. LaGory
A1 Hani Choudhry
A1 Amato J. Giaccia
A1 William J. Greenleaf
A1 Howard Y. Chang
YR 2018
UL http://biorxiv.org/content/early/2018/08/10/310359.abstract
AB 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.